Fact-checked by Grok 2 weeks ago

Precursor cell

A , also termed a , is a partially differentiated biological that retains proliferative but is committed to developing into one or more specific mature types, bridging the gap between multipotent stem cells and terminally differentiated cells. Unlike stem cells, which exhibit extensive self-renewal and broad potency, precursor cells undergo limited divisions and follow restricted lineages determined by intrinsic genetic programs and extrinsic signals. This commitment arises through progressive epigenetic modifications and transcriptional regulation that lock in cell fate during embryogenesis and adult tissue homeostasis. Precursor cells play roles in , , and repair across various systems, such as hematopoietic precursors generating cells in or neural precursors contributing to . In hematopoiesis, for instance, multipotent precursors differentiate sequentially into lineage-specific blasts like myeloblasts, which into granulocytes or monocytes under . Dysregulation of precursor or underlies pathologies including leukemias, where malignant blasts accumulate to blocked maturation, highlighting their causal in oncogenesis via genetic disrupting checkpoints. Therapeutic targeting of precursor cells holds promise for regenerative medicine, as seen in efforts to expand hematopoietic progenitors for transplantation or harness oligodendrocyte precursors for remyelination in demyelinating diseases, though challenges persist in achieving stable expansion without tumorigenic risk. Empirical studies emphasize that precursor potency is not merely environmental but rooted in causal molecular hierarchies, underscoring the need for precise lineage tracing in research to distinguish true progenitors from artifacts of culture conditions.

Definition and Fundamental Characteristics

Biological Definition and Properties

Precursor cells, also termed progenitor cells, represent an intermediate stage in cellular differentiation, positioned downstream from multipotent or pluripotent stem cells and upstream from terminally differentiated mature cells. They are characterized by a commitment to a specific developmental lineage, retaining a finite capacity for mitotic division to amplify cell numbers while progressing toward specialization, but lacking the indefinite self-renewal potential that defines true stem cells. This distinction arises from epigenetic and transcriptional restrictions that limit their potency, ensuring directed maturation rather than reversion to a more undifferentiated state. Key properties include proliferative responsiveness to extrinsic signals such as growth factors (e.g., or in neural contexts), which drive cell cycle progression via pathways like MAPK/ERK, coupled with an intrinsic program for asymmetric or symmetric division leading to differentiation. Unlike stem cells, precursor cells exhibit reduced telomere maintenance and accumulate senescence-associated markers with repeated divisions, typically undergoing 10-50 cycles before terminal differentiation, as observed in models of oligodendrocyte precursor cells. They express lineage-restricted molecular markers—such as Nestin and in early neural precursors or in hematopoietic progenitors—that facilitate identification and reflect partial commitment, while remaining plastic enough to respond to microenvironmental cues like or Wnt signaling for fate specification. In terms of functionality, precursor cells maintain by balancing and quiescence, often regulated by cyclin-dependent kinases (e.g., CDK4/6) and inhibitors like p21 or p27, preventing uncontrolled akin to neoplasia. Their differentiation potential is unipotent or oligopotent, yielding 1-4 subtypes per , as evidenced in adipocyte precursors differentiating solely into adipocytes under PPARγ . This constrained versatility underscores their in precise developmental timing, with disruptions linked to like leukemias, where aberrant evades differentiation checkpoints.

Distinction from Stem Cells and Mature Cells

Precursor cells represent an intermediate stage in , positioned between cells and fully differentiated cells within developmental hierarchies such as and . cells, defined by their for indefinite self-renewal and multipotency, serve as the foundational progenitors capable of generating diverse cell lineages while maintaining their through asymmetric or symmetric divisions. In , precursor cells lack robust self-renewal , exhibiting only proliferative divisions before committing to along restricted pathways; this arises from lineage-specific changes that preclude reversion to a multipotent . For example, hematopoietic cells (HSCs) can differentiate into multiple types while self-renewing, whereas downstream precursor cells like common myeloid progenitors are oligopotent, fated to produce granulocytes, monocytes, or erythrocytes/megakaryocytes with finite expansion. The distinction from mature cells further underscores the transitional nature of precursors. Mature cells are terminally differentiated, having lost proliferative capacity and acquired specialized functions tailored to tissue demands, such as oxygen transport in erythrocytes or phagocytosis in neutrophils, rendering them post-mitotic and incapable of further lineage progression. Precursor cells, however, retain mitotic activity to amplify populations prior to maturation; erythroblasts, for instance, undergo multiple divisions to generate sufficient numbers of red blood cells before enucleation, unlike the non-dividing reticulocytes and mature erythrocytes that follow. This proliferative phase in precursors ensures efficient tissue homeostasis and response to demand, as seen in the bone marrow where blast-like precursors expand under cytokine signals before differentiating into functional end cells.
CharacteristicStem CellsPrecursor CellsMature Cells
Self-renewal capacityIndefinite, via asymmetric divisionLimited, finite divisionsAbsent
Developmental potencyMultipotent or pluripotentOligopotent or unipotentNone (terminally differentiated)
Proliferative potentialHigh, sustainedModerate, lineage-restrictedNone (post-mitotic)
Functional maturityMinimal, undifferentiatedPartial, transitionalFull, specialized
These distinctions are empirically grounded in assays like colony-forming unit (CFU) tests, where stem cells form large, multilineage colonies indicative of broad potential, precursors yield smaller, lineage-specific clusters, and mature cells fail to form any. Such hierarchy ensures ordered development, with disruptions in precursor stages linked to disorders like leukemias, where immature blasts proliferate aberrantly without maturing.

Classification and Types

Hematopoietic Precursor Cells

Hematopoietic precursor cells, commonly referred to as hematopoietic progenitor cells (HPCs), are oligopotential intermediates derived from hematopoietic cells (HSCs) that commit to specific lineages with self-renewal . Unlike HSCs, which possess extensive self-renewal and multi-lineage long-term repopulation , HPCs exhibit transient proliferative potential and restriction to myeloid or lymphoid pathways. These cells reside primarily in the niche, where they respond to cytokines such as (SCF), interleukin-3 (IL-3), and (G-CSF) to amplify and into functional . HPCs are functionally defined by their to form colony-forming units (CFUs) in semi-solid assays, reflecting their for limited proliferation and ; for instance, CFU-GM progenitors yield granulocyte-macrophage colonies. Immunophenotypically, they express CD34 but often co-express lineage-specific markers: common myeloid progenitors (CMPs) are Lin⁻ Sca-1⁻ c-Kit⁺ CD34⁺ FcγRII/III⁻ CD16⁺ in mice, progressing to granulocyte-macrophage progenitors (GMPs; Lin⁻ Sca-1⁻ c-Kit⁺ CD34⁺ FcγRII/III⁺) and megakaryocyte-erythroid progenitors (MEPs; Lin⁻ Sca-1⁻ c-Kit⁺ CD34⁻ FcγRII/III⁻). In humans, analogous populations include CD34⁺ CD38⁺ subsets, with CMPs identified as CD45RA⁻ and GMPs as CD45RA⁺. lymphoid progenitors (CLPs) are marked by Lin⁻ IL-7Rα⁺ Flt3⁺ expression, committing to B, T, and lineages. These markers enable purification via for transplantation or , though functional assays confirm potency due to phenotypic overlap with HSCs. In steady-state hematopoiesis, HPCs bridge HSCs and mature cells by undergoing asymmetric divisions and cytokine-driven maturation, producing approximately 10¹¹–10¹² new blood cells daily in adults to maintain homeostasis. CMPs bifurcate into GMPs, which generate neutrophils, eosinophils, basophils, and monocytes under G-CSF or M-CSF influence, and MEPs, which differentiate into erythrocytes via erythropoietin (EPO) signaling and megakaryocytes yielding platelets through thrombopoietin (TPO). CLPs, influenced by IL-7 and Flt3 ligand, support adaptive immunity by populating lymphoid organs. Disruptions in HPC function, as seen in clonal disorders, underscore their role in rapid response to demand, such as post-hemorrhage or infection, where emergency granulopoiesis amplifies GMP output. Clinically, mobilized HPCs from peripheral blood, enriched via G-CSF, serve as grafts in over 90% of autologous transplants, demonstrating their repopulating efficacy despite shorter telomeres than bone marrow-derived counterparts.

Neural and Glial Precursor Cells

Neural precursor cells (NPCs) are multipotent progenitors in the (CNS) that self-renew and differentiate into neurons, , and , distinguishing them from more restricted types. These cells originate from neural cells during embryonic , primarily in the ventricular , where radial act as early progenitors facilitating both and gliogenesis. NPCs express markers such as Nestin, , and , reflecting their proliferative and multipotent . In the developing cortex, they undergo asymmetric divisions to expand the neural before committing to specific lineages, with predominating early and gliogenesis later. Glial precursor cells represent a more restricted , often emerging from NPC lineages via fate-switching , and are committed to producing and without neuronal potential. Glial-restricted precursors (GRPs), identified as early tripotent glial progenitors, express markers like A2B5 and can generate both astrocyte and oligodendrocyte lineages . A prominent example is oligodendrocyte precursor cells (OPCs), which comprise 5-10% of cells in the adult CNS, express PDGFRα and NG2 (CSPG4), and proliferate in response to demyelination for remyelination. Beyond differentiation, OPCs integrate into neural circuits by forming synapses with neurons and modulating activity, as evidenced by their responsiveness to glutamatergic and GABAergic inputs. In adult neurogenic niches, such as the (SVZ) and subgranular zone (SGZ), NPCs persist with multipotency, primarily generating rather than widespread neuronal , while glial precursors like OPCs maintain ongoing turnover for . This persistence supports and repair, though gliogenesis exceeds . Transcription factors like Qk regulate the neuro-to-gliogenic in progenitors, ensuring glial during late CNS . Disruptions in these precursors contribute to disorders like multiple sclerosis, where OPC fails, highlighting their causal in myelination .

Other Specialized Precursor Cells

In epithelial tissues, precursor cells such as those in the and commit to lineages producing , melanocytes, and fibroblasts. -derived precursors (SKPs), sourced from , exhibit self-renewal and multipotent differentiation potential, forming neural, mesodermal, and ectodermal derivatives including cells and Schwann cells under specific conditions. These cells, comprising approximately 0.3% of dermal fibroblasts in samples, and repair but diminish in regenerative with . Pancreatic precursor cells, in both embryonic and contexts, differentiate into endocrine and exocrine types, including insulin-producing cells. In models, these precursors express pancreatic duodenal 1 (PDX1) and nestin, progressing through stages marked by Nkx6.1 and Ngn3 expression to functional islet-like clusters capable of glucose-responsive insulin . multipotent precursors in and , comprising about 0.1-0.2% of dissociated cells, co-express ductal and endocrine markers like CK19 and , differentiation into hepatocytes, duct cells, and neurons , though their potency remains under . Hepatic precursor cells, distinct from broader stem populations, specifically generate hepatocytes and biliary epithelial cells (cholangiocytes) during regeneration. In rodent models of liver injury, oval cells—activated hepatic precursors—proliferate from periportal niches, expressing markers such as and , and reconstitute liver parenchyma with up to 30% hepatocyte repopulation in serial transplantation assays. Human equivalents, identified in diseased livers, similarly expand under proliferative stress but face challenges in isolation due to rarity (less than % of non-parenchymal cells) and ethical sourcing constraints. Mesenchymal-derived precursor cells in musculoskeletal tissues, such as pre-osteoblasts and pre-chondrocytes, arise from committed progenitors and undergo hypertrophy or mineralization. Pre-osteoblasts, marked by and expression, terminally differentiate into osteocytes, contributing to bone formation rates of approximately 0.5-1% turnover in adult trabecular . These lineages highlight the role of precursor cells in tissue-specific , though their therapeutic is limited by incomplete lineage in non-hematopoietic systems.

Biological Functions and Mechanisms

Role in Cellular Differentiation and Lineage Commitment

Precursor cells function as committed progenitors that bridge multipotent cells and terminally differentiated cells, undergoing progressive restriction of developmental potential during lineage to specific cell types. This entails the irreversible suppression of differentiation pathways through coordinated transcriptional, epigenetic, and signaling , enabling precursors to amplify and specialize within a defined lineage while losing pluripotency. In , precursor cells respond to extrinsic cues such as cytokines and niche signals, which activate lineage-specific programs, ensuring causal in tissue-specific output. Key mechanisms of lineage commitment in precursor cells involve transcription factors that both promote target fates and actively repress competitors, often reinforced by epigenetic modifications like and remodeling. For instance, signaling pathways such as Notch1, triggered by ligands like delta-like 4 in the thymic niche, instruct hematopoietic precursors to commit to the T-cell lineage by suppressing B-cell potential and driving β-selection at early stages. Similarly, in myeloid lineages, hematopoietic stem cells can transition to restricted precursors like common myeloid progenitors (CMPs) or pre-megakaryocyte-erythroid progenitors (PreMEs) without cell division, as evidenced by 30% of transplanted mouse HSCs downregulating Sca-1 within 36 hours and expressing lineage-specific genes in G0/G1 phases. These processes highlight how commitment precedes proliferation in some cases, with precursors losing multipotency—e.g., 92% of PreMegs forming only megakaryocytes in vitro—through downregulation of self-renewal genes. In lymphoid lineages, commitment occurs early in precursor stages; for B-cell development in mouse bone marrow, it precedes D_H-J_H recombination, as fractions A1 and A2 precursors (B220+ with germline IgH transcription) lack myeloid, erythroid, T, or NK potential, unlike earlier fraction A0 cells. Human + precursors seeding the thymus similarly progress through ++ common lymphoid progenitors to T-lineage restricted cells via IL-7 support for survival and reduced for αβ differentiation. These lineage-specific commitments ensure efficient differentiation, with precursors proliferating under growth factor influence (e.g., IL-7 for T cells) to generate mature effectors, maintaining homeostasis by balancing self-renewal loss with specialization. Such mechanisms underscore the deterministic role of environmental and intrinsic signals in directing precursor fate, independent of stochastic models in well-defined systems.

Contributions to Tissue Homeostasis and Regeneration

Precursor cells play a critical role in tissue homeostasis by serving as an intermediate population between stem cells and mature differentiated cells, enabling the continuous replacement of senescent or apoptotic cells to preserve tissue function and structure. In steady-state conditions, these cells respond to local signals such as cytokines and growth factors within their niches, undergoing limited proliferation and lineage-specific differentiation to match physiological demands without excessive expansion. For instance, in the hematopoietic system, precursor cells derived from hematopoietic stem cells (HSCs) generate approximately 10^11 new blood cells daily in adult humans, including erythrocytes for oxygen transport and platelets for hemostasis, thereby maintaining circulatory homeostasis. In epithelial tissues, precursor cells contribute to homeostasis through high-turnover renewal processes. In the intestinal epithelium, crypt-based progenitor cells—considered precursors to enterocytes, goblet cells, and other lineages—proliferate every 4-5 days to replace the villus epithelium, preventing barrier dysfunction and supporting amid constant shedding. Similarly, in the lung, basal progenitor cells and other precursors maintain alveolar and airway epithelia by differentiating into type II pneumocytes and cells, ensuring and during wear. Regarding regeneration, precursor cells are activated by injury-induced signals like inflammation or hypoxia, amplifying their proliferation to repair damage and restore tissue integrity. In skeletal muscle, muscle-resident progenitor cells (e.g., satellite cell-derived precursors) fuse with damaged myofibers or form new ones post-injury, contributing to functional recovery as observed in models of toxin-induced necrosis where regeneration restores up to 90% of fiber cross-sectional area within weeks. In the central nervous system, oligodendrocyte precursor cells (OPCs) participate in remyelination after demyelinating insults, differentiating into oligodendrocytes to repair axonal insulation, though their efficiency diminishes with age or repeated injury due to epigenetic barriers. These contributions are tightly regulated to prevent dysregulation, such as overproliferation leading to or ; for example, niche-derived factors like Wnt and signaling precursor quiescence and in multiple tissues. Disruptions in precursor , as seen in aging, impair —evidenced by reduced hematopoietic output in elderly individuals, where precursor pool exhaustion correlates with exceeding 10% in those over 65.

Historical Context and Discovery

Early Observations in Hematopoiesis

In the mid-19th century, microscopic examinations revealed the as the primary of , shifting understanding from earlier views implicating the and liver. Giulio Bizzozero, in , described myeloid and megakaryocytes—large precursor cells destined for platelet formation—in , proposing a continuous generative involving cells maturing into erythrocytes and leukocytes. Independently, observed in –1870 that leukocytes originate from "lymphoid marrow cells" in the , noting transitional forms that evolve into granular and nongranular , thus establishing a precursor-maturation sequence. These findings highlighted the presence of morphologically distinct immature precursors, though initial descriptions relied on unstained or basic preparations, limiting granularity resolution. Neumann's work further suggested a common origin for myeloid and erythroid lineages from these marrow precursors, anticipating later lineage commitment concepts. By the 1870s, observations in pathological states, such as leukemia, amplified visibility of blast-like precursors in human marrow, reinforcing normal hematopoiesis as involving proliferative immature stages. Advancements in staining techniques by in 1879–1880 enabled precise of precursor stages. Using dyes, Ehrlich visualized granule-containing myeloid precursors (e.g., early granulocytes with heterophilic, eosinophilic, or basophilic affinities) and nucleated erythroid forms, establishing differential cytology that delineated maturation pathways from promyelocytes to segmented neutrophils and from early erythroblasts to reticulocytes. These methods confirmed precursors' roles in steady-state and , laying groundwork for classifying hematopoietic lineages.

Evolution of Identification Methods

Initial identification of precursor cells depended on morphological criteria via light microscopy, distinguishing them from mature cells by features such as large nuclei, high nuclear-to-cytoplasmic ratios, and scant cytoplasm, as described in early 20th-century hematological studies by pathologists like Alexander Maximow. These observations laid groundwork for recognizing blasts and immature forms in bone marrow smears, though lacked functional validation. Functional assays emerged in the mid-20th century, with the 1961 spleen (CFU-S) assay by James and McCulloch marking a pivotal advance, demonstrating proliferative potential of hematopoietic progenitors through colony formation in irradiated mice. (CFU) assays followed, quantifying lineage-committed precursors like CFU-GM (granulocyte-macrophage) via semisolid cultures initiated in the 1960s, enabling enumeration based on differentiation . Advancements in immunophenotyping during the 1970s-1980s leveraged monoclonal antibodies and fluorescence-activated (FACS) to isolate precursors using surface markers; for instance, expression identified hematopoietic progenitors, refining populations beyond morphology. Long-term culture-initiating (LTC-IC) assays, developed in the 1980s, assessed primitive precursors by their to sustain hematopoiesis on stromal layers over weeks. Molecular techniques transformed from the onward, with and models purifying hematopoietic stem/ cells via combinations like CD34+CD38- phenotypes. Single-cell RNA sequencing, gaining prominence post-2010, now dissects precursor heterogeneity, revealing transcriptional states and trajectories in hematopoiesis and without functional . These methods, while powerful, require with functional readouts to confirm precursor potency, as immunophenotypes alone can overlap with non-progenitors.

Medical and Pathological Significance

Involvement in Hematological and Oncological Disorders

Precursor cells play a central role in hematological disorders such as (AML), where clonal of undifferentiated myeloid blasts— precursor cells—exceeds % of nucleated cells, disrupting hematopoiesis and leading to cytopenias. This accumulation arises from in hematopoietic stem or progenitor cells (HSPCs), self-renewal and blocked , with leukemic stem cells (LSCs) originating from these precursors sustaining and . Similarly, in (ALL), precursor lymphoid neoplasms involve of B- or T-cell progenitors, characterized by in and blood. In myelodysplastic syndromes (MDS), precursor cells exhibit and ineffective hematopoiesis due to clonal abnormalities in HSPCs, resulting in peripheral cytopenias despite hypercellular , with increased percentages signaling progression to AML. Clonal hematopoiesis of indeterminate potential (), involving in HSPC-derived clones, precedes MDS and AML, with rising to over 10% in individuals aged 70 and , conferring elevated through cumulative genetic . Oncogenic in these disorders often stems from stepwise in precursor cells, such as in TP53 or DNMT3A, fostering advantages and evasion of . Therapeutically, targeting precursor-derived LSCs remains challenging due to their quiescence and niche , though agents like exploit metabolic vulnerabilities shared with blasts. In , BCR-ABL in myeloid precursors drives , reversible by inhibitors, highlighting lineage-specific oncogenic dependencies. Overall, dysregulated precursor cell underscore the premalignant progression from conditions like CHIP to overt hematological malignancies, informing via .

Applications in Diagnosis and Monitoring

Flow cytometric immunophenotyping of bone marrow or peripheral blood samples enables the identification and classification of abnormal hematopoietic precursor cells in acute leukemias, distinguishing precursor B-cell acute lymphoblastic leukemia (B-ALL) from precursor T-cell ALL and acute myeloid leukemia (AML) based on aberrant antigen expression patterns such as CD19, CD10, and CD34 for B-precursors or CD13 and CD33 for myeloid blasts. In AML diagnosis, morphological examination reveals precursor blasts comprising at least 20% of nucleated cells, often featuring Auer rods as pathognomonic inclusions confirming myeloid lineage. This approach surpasses traditional microscopy by quantifying precursor cell subsets and detecting leukemia-associated immunophenotypes (LAIPs) with multi-parameter analysis. For monitoring treatment response and relapse risk, multiparametric assesses (MRD) by detecting persistent leukemic precursor cells at sensitivities down to 0.01%, correlating MRD levels post-induction with event-free in B-precursor ALL; undetectable MRD by predicts lower rates in multicenter studies. Standardized eight-color protocols facilitate high-sensitivity MRD tracking in virtually all B-cell precursor ALL cases when analyzing over 4 million cells, enabling risk-stratified adjustments. In precursor hematologic conditions like monoclonal B-cell lymphocytosis or clonal hematopoiesis, serial monitors progression to overt by tracking expanding abnormal precursor populations. Emerging methods, such as single-cell sequencing-integrated (e.g., SWIFT-seq), enhance of plasma cell precursors in smoldering for early .

Therapeutic Potential and Clinical Applications

Use in Bone Marrow and Stem Cell Transplantation

Hematopoietic precursor cells, encompassing committed progenitors such as those expressing , serve as components in and hematopoietic stem cell transplantation (HSCT) by facilitating the reconstitution of following myeloablative . These cells are typically sourced from donor via , granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral through , or umbilical cord , and are infused intravenously to repopulate the ablated marrow. In autologous HSCT, the recipient's own precursor cells are harvested and reinfused, while allogeneic HSCT utilizes HLA-matched donor cells to restore hematopoiesis in conditions like , , and . The quantity of CD34+ precursor cells in the graft is a determinant of engraftment success, with doses of 5–7 × 10^6 cells per kg of recipient weight linked to superior overall survival and decreased transplant-related mortality compared to lower doses below 5 × 10^6/kg. Peripheral blood grafts, enriched in short-term progenitors due to mobilization, enable faster hematopoietic recovery—neutrophil engraftment (absolute neutrophil count >500/μL) occurs in 7–14 days versus 10–21 days for bone marrow grafts—reducing vulnerability to infections and hemorrhage during the post-transplant aplasia. Post-infusion, precursor cells to the niche via multistep processes involving signaling (e.g., /SDF-1 to ), selectin-mediated rolling, integrin-dependent firm , and cytoskeletal rearrangements like podosome formation for intravasation through . Successful engraftment of these progenitors supports transient output, bridging until long-term hematopoietic cells establish durable multilineage reconstitution, with rates influenced by factors such as graft and recipient .

Experimental Regenerative Therapies

Neural precursor cells (NPCs), derived from fetal or induced pluripotent cells (iPSCs), have been investigated in preclinical models for (SCI) repair, where transplantation promotes functional through into neurons and , as well as paracrine effects enhancing endogenous repair. In SCI models, NPC grafts integrated into and supported axonal regrowth, though long-term remains by immune rejection and incomplete maturation. A I/IIa initiated in 2016 tested fetal-derived NPCs in 10 patients with progressive , reporting modest improvements in visual and sensory evoked potentials at 2-year follow-up, attributed to reduced and remyelination, without severe adverse . Oligodendrocyte precursor cells (OPCs), the progenitors of myelin-producing , are a for remyelination therapies in demyelinating diseases like . Preclinical studies using iPSC-derived OPCs in mouse models of spinal cord demonstrated robust remyelination of demyelinated axons, with grafted cells surviving and differentiating efficiently when combined with immunosuppressive regimens. CRISPR-edited embryonic stem cell-derived OPCs, engineered to resist remyelination inhibitors, enhanced myelin repair in hypomyelinated shiverer mouse upon transplantation in 2024 experiments, highlighting potential to overcome inhibitory microenvironments. Pharmacological augmentation, such as , stimulated OPC and remyelination in cuprizone-induced demyelination models by activating differentiation pathways, suggesting adjunctive strategies to endogenous OPCs without cell transplantation. Skin-derived precursors (SKPs), multipotent adult stem-like cells from dermal sources, show promise in neural regeneration due to their accessibility and neural crest origin, differentiating into Schwann cells for peripheral nerve repair in preclinical assays. In vitro and rodent studies from 2018 confirmed SKPs' self-renewal and trilineage potential (neural, mesenchymal, melanocytic), with applications explored for skin wound healing and neurodegenerative conditions via paracrine signaling. However, clinical translation lags, with no large-scale trials reported by 2025, underscoring challenges in scalability, potency consistency, and tumorigenicity risks inherent to progenitor populations. Overall, these therapies remain experimental, with efficacy tied to precise timing, dosing, and microenvironment modulation, as evidenced by variable outcomes in animal models where inflammation hinders integration.

Research Advances and Methodological Developments

Single-Cell Sequencing and Atlases

Single-cell sequencing (scRNA-seq) has transformed the of precursor cells by resolving transcriptomic heterogeneity at the level, particularly in hematopoietic stem and progenitor cells (HSPCs), which were previously averaged in analyses. This approach captures dynamic changes during , identifying continuous trajectories rather than discrete stages and uncovering multipotent subpopulations with myeloid or lymphoid biases. For example, early hematopoiesis studies using scRNA-seq on pluripotent stem cell-derived progenitors revealed oxidative shifts linked to . advances, including droplet-based methods like , have scaled to thousands of cells, pseudotime to model precursor progression. In hematopoiesis, scRNA-seq has delineated HSPC landscapes, showing cell cycle progression influences lineage-specific gene expression in precursors under stress conditions. A 2019 analysis of human bone marrow CD34+ cells stratified progenitors into hierarchical clusters, highlighting transcriptional continuity from stem to mature lineages. Recent multimodal integrations, combining scRNA-seq with or , further refine potency assessments; a 2024 immunophenotype-coupled atlas of progenitors identified functionally distinct subtypes via cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq). These findings challenge prior models of rigid branching, emphasizing plasticity influenced by microenvironmental cues like bone marrow niches. Single-cell atlases compile these into comprehensive maps of precursor . The single-cell resolution atlas of HSPC (2021) traced ontogenetic trajectories , revealing transcriptomic shifts during niche . In mice, a 2024 time-resolved model of bone marrow hematopoiesis tracked HSPC over weeks, integrating scRNA-seq with tracing to quantify output efficiencies. efforts, such as the Atlas of Hematopoietic Stem Cell , provide ontogeny-spanning profiles of HSPCs from fetal liver to adult marrow, aiding of age-related declines in precursor . These resources, often deposited in public like GEO, facilitate cross-species comparisons and predictive modeling of precursor .

Insights from Model Organisms and In Vitro Studies

In mice, lineage tracing using Confetti reporter transgenes combined with binomial modeling of clonal variability has quantified hematopoietic precursor contributions, revealing that steady-state adult hematopoiesis draws from thousands of hematopoietic stem and progenitor cells (HSPCs), while embryonic HSPCs number in the hundreds with limited fetal expansion. This approach highlights clonal dynamics post-perturbation, such as after 5-fluorouracil treatment, where precursor numbers decline, and in Fanconi anemia models (Fancc^{-/-}), where counts remain normal despite impaired regeneration. C. elegans provides deterministic insights into precursor fate via its invariant , where six vulval precursor cells (P3.p to P8.p) undergo inductive signaling from the anchor to specify vulval fates, with (LIN-12) mediating lateral inhibition and GLP-1 regulating germline precursors in the niche. Laser ablation experiments confirm that - interactions dictate precursor competence, underscoring hardwired developmental programs absent in more stochastic systems. In Drosophila, imaginal disc precursors proliferate during larval stages to form adult appendages, with maternal gradients (e.g., Bicoid) and homeotic selectors (e.g., in the bithorax complex) imposing segmental identity on these pools, as revealed by genetic mosaics and temperature-sensitive mutants. precursors asymmetrically divide to yield ganglion mother cells, conserving asymmetric segregation mechanisms seen across bilaterians. Zebrafish models expose precursor dynamics in neurogenesis, where HuC homolog expression labels neuronal precursors from the neural plate stage (10.5 hours post-fertilization), enabling live imaging of proliferation in radial glia and misspecification in mutants like zc4h2 knockouts, which reduce GABAergic interneuron output. Leukotriene C4 signaling via cysltr1 further boosts precursor proliferation post-injury, linking lipid mediators to regenerative competence. In vitro cultures of human HSPCs have mapped continuous differentiation trajectories, showing CD273^{high} subsets upregulate stemness genes (e.g., Thy1, HOPX) while committing to lineages, as tracked via single-cell in serum-free media. UM171 supplementation enhances clonal self-renewal in erythroid-megakaryocyte-mast precursors, shifting output toward mast cells (33% progenitors vs. 13% in controls) through LSD1-CoREST1 degradation, /SPI1 activation, and a stem-like transcriptome. Stromal-free assays further identify aryl hydrocarbon receptor (AhR) as a suppressor of multilineage output, with TCDD activation reducing erythroid and myeloid yields by 50-70%. Protocols coculturing mononuclear cells with cytokines (e.g., SCF, FLT3L) induce precursor transdifferentiation to endothelial lineages, marked by / expression and tube formation, confirming vascular potential under . For lymphoid commitment, OP9-DLL1/4 monolayers or artificial thymic organoids drive T-cell maturation from precursors, recapitulating Notch-dependent beta-selection with 20-40% . These systems isolate extrinsic cues, revealing dosage-dependent effects of small molecules like UM171 on potency without niche confounders.

Controversies and Open Debates

Disputes on Differentiation Plasticity and Transdifferentiation

The concept of plasticity in precursor cells refers to the potential for these partially committed progenitors to alter their developmental in response to environmental cues or , while implies a direct switch to an unrelated without reverting to a pluripotent . Early claims of such plasticity, particularly in adult tissue-specific precursors like hematopoietic or neural progenitors, sparked debate, with proponents citing in vitro reprogramming experiments where precursors adopted alternative fates under forced expression of transcription factors. However, skeptics argue that true plasticity is exceedingly rare in committed precursors due to epigenetic barriers and lineage-specific gene repression, which stabilize cell identity and limit fate changes without dedifferentiation to a stem-like . A major point of contention involves artifactual explanations for observed crossing, such as events where a precursor merges with a host cell, acquiring hybrid properties misinterpreted as . For instance, studies on bone marrow-derived precursors contributing to non-hematopoietic tissues, like hepatocytes or cardiomyocytes, were initially hailed as evidence of but later attributed largely to rather than genuine , with rates exceeding 10-50% in some experimental setups. Critics, including analyses from 2003 onward, emphasize that without rigorous controls for —such as using Cre-lox tracing—such data overstate precursor versatility, as pure precursor populations fail to replicate these outcomes consistently. This skepticism extends to protocols, where induced changes in precursors (e.g., fibroblasts to neurons) often revert or require ongoing exogenous factors, questioning physiological relevance. In vivo evidence further fuels disputes, as lineage tracing in model organisms reveals that precursor is context-dependent and often mediated by residual contamination rather than intrinsic progenitor reprogrammability. For example, in intestinal or gastric epithelia, apparent of mature precursors during is debated as either adaptive plasticity under stress or misattributed from cryptic stem cells, with single-cell RNA sequencing showing persistent lineage biases. Proponents of limited plasticity acknowledge rare, injury-induced shifts—such as in limb regeneration where precursors exhibit broader potency—but contend these are evolutionarily specialized and not generalizable to mammalian precursors without genetic manipulation. Opponents highlight that overinterpreting such events risks inflating therapeutic hype, as stable, efficient in precursors remains unproven beyond lab artifacts. These debates underscore methodological challenges, including distinguishing plasticity from heterogeneity within precursor pools or experimental noise, with calls for standardized assays integrating and long-term tracing to resolve whether represents causal adaptability or exceptional outliers. While some fields, like , invoke precursor to explain tumor heterogeneity (e.g., in blasts), verification requires discounting biases toward positive reporting in high-impact journals. Ultimately, empirical data favor viewing precursor as constrained by developmental hierarchies, with feasible only under non-physiological conditions.

Challenges in Precise Identification and Potency Assessment

Marker-based identification of precursor cells, particularly in hematopoietic and neural lineages, faces significant hurdles due to the absence of lineage-specific, universally reliable surface antigens. For instance, expression, commonly used to enrich hematopoietic precursor cells, labels a broad spectrum of progenitors with varying capacities, leading to with non-precursor populations and incomplete of target cells. Similarly, in mesenchymal and precursor contexts, markers like PDGFRα fail to delineate pure subpopulations amid tissue heterogeneity, complicating purification and risking misidentification of committed versus multipotent states. These limitations arise from overlapping expression profiles across developmental stages, exacerbated by environmental influences that dynamically alter marker phenotypes, as observed in single-cell analyses of B-cell precursors where shared transcriptional programs hinder precise precursor tracing. Functional validation through prospective assays, such as limiting dilution transplants or lineage tracing, provides stronger evidence of precursor identity but is invasive, low-throughput, and ethically constrained in human studies, often relying on surrogate animal models with species-specific discrepancies. In oncogenic settings, such as early T-cell precursor acute lymphoblastic leukemia, morphological and immunophenotypic overlap with normal thymic precursors delays diagnosis, with heterogeneous mutations further obscuring precursor-specific signatures despite advanced flow cytometry. Assessing precursor cell potency—defined as their capacity for self-renewal and multilineage —encounters parallel obstacles, primarily from the qualitative and variable nature of gold-standard assays like (CFU) enumeration for hematopoietic progenitors. These assays require 10-14 days of culture, exhibit high inter-laboratory variability due to media inconsistencies and subjective colony scoring, and fail to capture long-term repopulation potential, rendering them inadequate for rapid clinical potency release testing. differentiation protocols, while scalable, often underestimate true potency owing to incomplete recapitulation of niches, with donor-specific factors introducing up to 10-fold variability in output, as quantified in mesenchymal precursor immunomodulatory assays. Quantitative molecular proxies, such as for pluripotency factors (e.g., OCT4, ), correlate imperfectly with functional potency and are confounded by epigenetic noise or culture-induced artifacts, necessitating orthogonal validation that multiplies assay complexity and cost. Emerging single-cell potency metrics aim to address these gaps but currently lack standardization, highlighting persistent challenges in translating preclinical assessments to reproducible therapeutic outcomes.

References

  1. [1]
    Progenitor Cells Explained: Types & Clinical Uses
    Jan 24, 2024 · Every cell in the human body, and that of other mammals, originates from stem cell precursors. Progenitor cells are descendants of stem cells ...
  2. [2]
    Comparison between Stem Cell and Progenitor Cell.
    Progenitor cell are very similar to stem cells. They are biological cells and like stem cells, they too have the ability to differentiate into a specific type ...
  3. [3]
    The Biochemistry of Hematopoietic Stem Cell Development - PMC
    The description of the complete genetic program of the nascent HSC and its direct precursor cell, the hemogenic endothelium, would open new possibilities ...
  4. [4]
    The hematopoietic stem cell and its niche: a comparative view
    A precursor cell type is usually, although not always, post-mitotic, but has the capacity to assume one of several differentiated fates. As an example, the ...
  5. [5]
    An integrated global regulatory network of hematopoietic precursor ...
    The mouse bone marrow-derived EML cell is a multi-potential hematopoietic precursor cell model that can differentiate into erythroid, myeloid, and lymphoid ...
  6. [6]
    Hemopoiesis - How Blood Cells are Made - Interactive-Biology.com
    The precursor cell hemocytoblast may either divide to become other hemocytoblasts or become either a myeloid stem cell or a lymphoid stem cell. Lymphoid Stem ...
  7. [7]
    Stem Cell Reports
    May 25, 2017 · Oligodendrocyte precursor cells (OPCs) offer considerable potential for the treatment of demyelinating diseases and injuries of the CNS.
  8. [8]
    Stem cell: what's in a name? - Nature
    as well as ...
  9. [9]
    A glossary for stem-cell biology - Nature
    Jun 28, 2006 · Founder/ancestor/precursor cell General terms for cell without self-renewal ability that contributes to tissue formation. In some cases they ...<|separator|>
  10. [10]
    Modeling the dynamics of oligodendrocyte precursor cells and the ...
    Mar 28, 2018 · Oligodendrocyte precursor cells (OPCs) have remarkable properties: they represent the most abundant cycling cell population in the adult ...
  11. [11]
    Proliferation and differentiation of rat neuroepithelial precursor cells ...
    ... Markers that are expressed in the proliferating neuronal precursor are ... Proliferation and differentiation of rat neuroepithelial precursor cells in vivo.
  12. [12]
    Regulation of proliferation and differentiation of adipocyte precursor ...
    In mammals, primary cell cultures have contributed to unraveling the major processes involved in adipogenesis, such as the proliferation of precursor cells and ...
  13. [13]
    Differential Regulation of Proliferation and Differentiation in Neural ...
    Neuronal precursor cells (NPCs) are temporally regulated and have the ability to proliferate and differentiate into mature neurons, oligodendrocytes, ...<|control11|><|separator|>
  14. [14]
    Biology of stem cells: an overview - PMC - NIH
    Aug 15, 2011 · Stem cells are defined as precursor cells that have the capacity to self-renew and to generate multiple mature cell types.
  15. [15]
    Adult Stem Cells - NCBI
    Unlike stem cells, precursors and other subsequent intermediates generally undergo limited self-renewal in vivo and are committed to a pathway of ...Missing: distinction | Show results with:distinction
  16. [16]
    Hematopoiesis: Definition, Types & Process - Cleveland Clinic
    It's called a hematopoietic stem cell (HSC). An HSC develops into a precursor cell, or “blast” cell. A precursor cell is on track to become a specific type ...What Is Hematopoiesis? · What Blood Cells Get Made... · Mononuclear Cell Production<|control11|><|separator|>
  17. [17]
    Histology, Hematopoiesis - StatPearls - NCBI Bookshelf - NIH
    The precursors go on to form mature basophils, neutrophils, and eosinophils respectively. Owing to the overall predominance of neutrophils compared to these ...
  18. [18]
    Hematopoiesis - PMC - PubMed Central - NIH
    An 'endothelium with hemogenic properties' was first described as being the precursor to HSCs at the end of the 1800s (reviewed by Adamo and García-Cardeña, ...
  19. [19]
    Stem cells: past, present, and future
    Feb 26, 2019 · Somatic or adult stem cells are undifferentiated and found among differentiated cells in the whole body after development. The function of these ...
  20. [20]
    https://www.ptglab.com/news/blog/hematopoietic-stem-and-progenitor-cells-hspcs-what-they-are-and-how-to-identify-them/
  21. [21]
    Hematopoietic stem and progenitor cells - PubMed
    Hematopoietic stem and progenitor cells (HSPCs) are a rare population of precursor cells that possess the capacity for self-renewal and multilineage ...
  22. [22]
    Myeloid cell origins, differentiation, and clinical implications - PMC
    Apr 1, 2017 · The Common Myeloid Progenitor (CMP) and the Common Lymphoid Progenitor (CLP) give rise to the two mains arms of the hematopoietic hierarchy. ...
  23. [23]
    Hematopoietic Stem and Progenitor Cells (HSPCs)
    The cells are then assessed by flow cytometry to identify cells expressing hematopoietic markers, notably CD34, CD45, and CD43, and their ability to generate ...
  24. [24]
    [PDF] Human Hematopoietic Stem and Progenitor Cell Phenotypes ...
    Megakaryocyte-Erythroid Progenitor (MEP)3,4,8,13,14,20. Arises from CMPs ... GMP: Granulocyte-Macrophage Progenitor; HSC: Hematopoietic Stem Cell; HSPC ...
  25. [25]
    Concise Review: Evidence for CD34 as a Common Marker for ... - NIH
    This review presents evidence establishing CD34 as a general marker of progenitor cells. We explore common traits, such as marker expression, morphology and ...
  26. [26]
    Stem and progenitor cells: origins, phenotypes, lineage ... - PubMed
    It is interesting that in the hematopoietic system the only long-term self-renewing cells in the stem and progenitors pool are the hematopoietic stem cells.
  27. [27]
    Myeloid Lineage Commitment from the Hematopoietic Stem Cell
    Jun 22, 2007 · The CMP differentiates into the GMP and the MEP. The CMP can generate all types of myeloid colonies, whereas the GMP or the MEP produces ...
  28. [28]
    Hematopoietic progenitor cells as integrative hubs for adaptation to ...
    Jan 1, 2020 · Herein, we review emerging evidence that the adaptation of hematopoietic progenitor cells to inflammation acts as a central hub of the host ...
  29. [29]
    HEMATOPOIETIC PROGENITOR CELLS (HPC) FROM MOBILIZED ...
    HEMATOPOIETIC PROGENITOR CELLS (HPC) FROM MOBILIZED PERIPHERAL BLOOD DISPLAY ENHANCED MIGRATION AND MARROW HOMING COMPARED TO STEADY-STATE BONE MARROW HPC.
  30. [30]
    Neural stem and progenitor cells in health and disease - PMC - NIH
    We will define NSPCs to be any self-renewing neural cells capable of differentiation to neurons, astrocytes and/or oligodendrocytes.
  31. [31]
    Differential transformation capacity of neuro-glial progenitors during ...
    Radial glia comprise a molecularly defined cellular population playing critical roles in CNS development as both neural and glial progenitors (8, 9) and as ...
  32. [32]
    https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/cell-culture-and-cell-culture-analysis/imaging-analysis-and-live-cell-imaging/neural-stem-cell-markers-antibodies
  33. [33]
    Regulation of Neural Progenitor Cell Development in the Nervous ...
    We review the current state of understanding of progenitor cell diversity within the cortical ventricular zone (VZ) and then describe how lateral signaling via ...
  34. [34]
    Glial restricted precursor cells in central nervous system disorders
    Among these precursors, glial-restricted precursor cells (GRPs) are considered the earliest glial progenitors and exhibit tripotency for both Type I/II ...
  35. [35]
    Glial restricted precursor cells in central nervous system disorders
    Oct 14, 2020 · Among these precursors, glial-restricted precursor cells (GRPs) are considered the earliest glial progenitors and exhibit tripotency for both ...
  36. [36]
    Oligodendrocyte precursor cells: the multitaskers in the brain - PMC
    Jul 4, 2023 · OPCs have multiple functions beyond their role as progenitors, exerting control over neural circuits and brain function through distinct pathways.
  37. [37]
    Identifying the functions of two biomarkers in human ...
    May 1, 2021 · Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating ...Rna-Seq For The... · Fig. 3 · Abbreviations<|separator|>
  38. [38]
    Cell of all trades: oligodendrocyte precursor cells in synaptic ...
    OPCs are electrically sensitive, form synapses with neurons, support blood–brain barrier integrity, and mediate neuroinflammation.
  39. [39]
    Neural Progenitor Cell Terminology - PMC - PubMed Central - NIH
    Dec 6, 2018 · Stem cells can be “pluripotent precursor cells” that give rise to all cell types within an organism, or “multipotent precursor cells” that have ...
  40. [40]
    Neural Progenitor Cell Terminology - Frontiers
    Here we review past and current terminology used to refer to NPCs, including embryonic and adult precursor cells of the cerebral cortex and hippocampus.Introduction · Embryonic Neural Progenitor... · Adult Neural Progenitor Cells
  41. [41]
    Identification of Qk as a Glial Precursor Cell Marker that ... - PubMed
    Oct 13, 2020 · During brain development, neural stem cells (NSCs) initially produce neurons and change their fate to generate glias.
  42. [42]
    Clinical application of oligodendrocyte precursor cells for cell-based ...
    Oct 18, 2016 · Oligodendrocyte precursor cells (OPCs), which give rise to mature oligodendrocytes (OLs), play important roles in maintaining white matter ...
  43. [43]
    The Human Skin-Derived Precursors for Regenerative Medicine
    Jul 11, 2018 · Skin-derived precursors (SKPs) are an adult stem cell source with self-renewal and multipotent differentiation.
  44. [44]
    Human skin stem cells and the ageing process - PubMed
    Multipotent cells (skin-derived precursor cells) are present in human dermis; dermal stem cells represent 0.3% among human dermal foreskin fibroblasts. A ...
  45. [45]
    Pancreatic Precursors and Differentiated Islet Cell Types From ...
    Aug 1, 2003 · ES cells were evaluated for their ability to differentiate into pancreatic and islet lineage-restricted stages including pancreatic duodenal ...
  46. [46]
    The Adult Mouse and Human Pancreas Contain Rare Multipotent ...
    Mar 4, 2011 · The search for putative precursor cells within the pancreas has been the focus of extensive research. Previously, we identified rare ...
  47. [47]
    Liver Stem Cell - an overview | ScienceDirect Topics
    The term liver or hepatic stem cell is used only for precursors of the two epithelial liver cell types, the hepatocytes and bile duct epithelial cells.
  48. [48]
    Stem cells in the adult pancreas and liver - PMC - PubMed Central
    Stem cells are undifferentiated cells that can self-renew and generate specialized (functional) cell types. The remarkable ability of stem cells to ...
  49. [49]
    Basics of Stem Cell Biology as Applied to the Brain - NCBI - NIH
    Jul 27, 2016 · Stem cells are usually categorized as multipotent (able to give rise to multiple cells within a lineage), pluripotent (able to give rise to all ...Missing: precursor | Show results with:precursor
  50. [50]
    Lineage commitment of hematopoietic stem cells and progenitors
    Jul 9, 2020 · The molecular mechanisms, cellular relationships and timing of lineage commitment are fundamental to the regulation of blood production in ...
  51. [51]
    Mechanisms underlying lineage commitment and plasticity of helper ...
    Feb 26, 2010 · A key aspect of commitment is that not only are genes turned on by transcription factors, but also that genes conferring alternative fates are ...
  52. [52]
    Molecular and Cellular Basis of T cell Lineage Commitment - PMC
    This review will focus on the characteristics of the hematopoietic progenitors which colonize the thymus and their subsequent commitment/ differentiation, both ...
  53. [53]
    Hematopoietic stem cells can differentiate into restricted myeloid ...
    May 15, 2018 · Our results reveal that HSCs are able to differentiate into restricted progenitors, especially common myeloid, megakaryocyte-erythroid and pre-megakaryocyte ...
  54. [54]
    Commitment to the B Lymphoid Lineage Occurs before D H
    Together, these data indicate that pre–pro-B cells, defined as Frs. A1 and A2, lack NK and T lymphoid as well as myeloid and erythroid lineage precursor cells, ...
  55. [55]
    Hematopoietic Precursor Cell Cell Types - CZ CELLxGENE CellGuide
    Hematopoietic precursor cells are multipotent cells that differentiate into blood cells, found in red bone marrow, and maintain a supply of new blood cells.
  56. [56]
    The hematopoietic stem cell niche in homeostasis and disease - PMC
    The stem cell niche generates signals that regulate HSC self-renewal, quiescence, and differentiation.
  57. [57]
    The Intestinal Stem Cell Niche: Homeostasis and Adaptations - PMC
    The ISC niche contains cells that provide a local source of signals that nourish stem cells to support tissue homeostasis, maintaining a crucial balance between ...<|separator|>
  58. [58]
    Lung Stem and Progenitor Cells in Tissue Homeostasis and Disease
    Endogenous adult lung stem/progenitor cells are regenerative cell populations important for epithelial cell maintenance and injury repair.
  59. [59]
    Contributions of muscle-resident progenitor cells to homeostasis ...
    Satellite cells, closely associated with myofibers, are established as the canonical muscle stem cell, with self-renewal and myofiber-regenerating capacity.
  60. [60]
    What Are the Roles of Oligodendrocyte Precursor Cells in Normal ...
    Nov 21, 2023 · They function as sensors of hypoxia and promote angiogenesis and respond to signals from astrocytes and microglia to contribute to ...
  61. [61]
    Maintaining tissue homeostasis: dynamic control of somatic stem ...
    Somatic stem cells have to respond to tissue damage and proliferate according to tissue requirements, while avoiding over-proliferation.
  62. [62]
    Hematopoietic stem cell discovery: unveiling the historical and future ...
    Jan 29, 2025 · This assay facilitates the identification, enumeration, and analysis of colonies formed by differentiated hematopoietic stem and progenitor cells (HSPCs)
  63. [63]
    Blood at 70: its roots in the history of hematology and its birth
    1868, Discovery of the role of the bone marrow in hematopoiesis by Neumann and independently by Bizzozero. 1868, Virchow describes leukemia, thrombosis, and ...<|separator|>
  64. [64]
    The origins of bone marrow as the seedbed of our blood
    Neumann also recognized that leukocytes were formed in the marrow and later postulated a common stem cell for all hematopoietic cells. This may have been his ...Missing: 1870 | Show results with:1870
  65. [65]
    Paul Ehrlich and the Early History of Granulocytes - ASM Journals
    Paul Ehrlich's techniques, published between 1879 and 1880, for staining blood films using coal tar dyes, and his method of differential blood cell counting,
  66. [66]
    Paul Ehrlich (1854-1915) and His Contributions to the Foundation ...
    Feb 5, 2016 · All in all, Paul Ehrlich demonstrated that blood cells are much more heterogeneous cells than had been assumed previously, thereby paving ...
  67. [67]
    [PDF] On the origin of hematopoietic stem cells: Progress and controversy
    Hematopoietic Stem Cells (HSCs) are generated during embryonic development, but their precise origins are still uncertain, despite being known for over 50 ...
  68. [68]
    The origins of the identification and isolation of hematopoietic stem ...
    First evidence of long-lived blood progenitor. Two years stand out as the starting point of the science that led to an understanding of hematopoietic stem cells ...<|control11|><|separator|>
  69. [69]
    Culture and Analysis of Hematopoietic Progenitor Cells in CFU Assays
    The colony-forming unit (CFU) assay is one of the most widely used assays for hematopoietic stem and progenitor cells (HSPCs). CFU assays allow measurement ...
  70. [70]
    Haematopoietic stem cells: past, present and future - Nature
    Feb 6, 2017 · The discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as ...
  71. [71]
    Assay systems for hematopoietic stem and progenitor cells - Bock
    Jun 4, 2009 · The potentials of these assays have been recently enhanced by the extended LTC and the switch LTC modifications. Although some hematopoietic ...
  72. [72]
    Resolving the hematopoietic stem cell state by linking functional and ...
    Aug 10, 2023 · In this review, we will give a historical overview of the functional and molecular assays in the field, identify new tools that combine molecular and ...
  73. [73]
    The genesis of human hematopoietic stem cells - ScienceDirect
    Aug 10, 2023 · Recent single-cell studies have helped in identifying the rare human HSCs at stages when functional assays are unsuitable for distinguishing ...
  74. [74]
    Acute Myeloid Leukemia - StatPearls - NCBI Bookshelf - NIH
    Apr 27, 2024 · AML is characterized by the clonal proliferation of undifferentiated myeloid precursors, known as blasts, within the bone marrow compartment.
  75. [75]
    Leukemic Stem Cells and Hematological Malignancies - MDPI
    Leukemia cells, particularly AML cells, represent an LSC subtype that originates from hematopoietic stem and progenitor cells (HSPCs). LSCs share functional and ...Leukemic Stem Cells And... · 2. Hematological... · 2.1. Leukemia
  76. [76]
    Classification of hematopoietic neoplasms - UpToDate
    Jan 12, 2024 · Precursor lymphoid neoplasms · Mature B cell neoplasms · Hodgkin lymphoma (HL) · Mature T cell or NK cell lineage.<|separator|>
  77. [77]
    Myelodysplastic Syndrome - StatPearls - NCBI Bookshelf - NIH
    Myelodysplastic syndrome (MDS) is a diverse collection of hematologic neoplasms characterized as a clonal disorder of hematopoietic stem cells.
  78. [78]
    Clonal hematopoiesis and hematological malignancy - PMC - NIH
    Oct 1, 2024 · Clonal hematopoiesis (CH), the expansion of hematopoietic stem cells and their progeny driven by somatic mutations in leukemia-associated genes, is a common ...
  79. [79]
    Hematopoietic stem cell aging and leukemia transformation | Blood
    Aug 10, 2023 · With aging, hematopoietic stem cells (HSCs) have an impaired ability to regenerate, differentiate, and produce an entire repertoire of mature blood and immune ...
  80. [80]
    Leukemic stem cells and therapy resistance in acute myeloid leukemia
    Feb 1, 2023 · This review discusses LSC biology and associated resistance mechanisms, potential therapeutic LSC vulnerabilities and current clinical trial activities.
  81. [81]
    The adventurous journey from hematopoietic to leukemic stem cells
    Apr 14, 2022 · A variety of hematological cancers, such as leukemias, are derived from hematopoietic stem and progenitor cells (HSPCs) by a stepwise ...
  82. [82]
    Myeloid Malignancy Precursor Conditions: What Fellows Need to ...
    The development of a myeloid malignancy such as MDS or acute myeloid leukemia (AML) involves a progression through several precursor disease states.
  83. [83]
    Flow cytometric immunophenotyping for hematologic neoplasms
    Apr 15, 2008 · Flow cytometric immunophenotyping remains an indispensable tool for the diagnosis, classification, staging, and monitoring of hematologic ...
  84. [84]
    Flow Cytometry in the Diagnosis of Leukemias - NCBI
    FCM immunophenotyping plays an important role in the classification of mature B-cell neoplasms. Each type of these diseases has some unique or relatively ...
  85. [85]
    Minimal residual disease detection using flow cytometry - NIH
    MRD detection on FCM platform requires detection of immune phenotype markers with selective positive expression on leukemic cells vis-a-vis negative expression ...
  86. [86]
    Standardized flow cytometry for highly sensitive MRD ...
    Standardized flow cytometry allows highly sensitive MRD measurements in virtually all BCP-ALL patients. If sufficient cells are measured (>4 million), ...
  87. [87]
    Value of flow cytometry for MRD-based relapse prediction in B-cell ...
    Dec 14, 2020 · FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.Mrd Analysis And... · Results · Undetectable Mrd By Fcm...
  88. [88]
    Dana-Farber Cancer Institute Unveils Groundbreaking Blood Test ...
    Aug 8, 2025 · ... diagnosis and monitoring of multiple myeloma (MM) and its precursor conditions. The new method, known as SWIFT-seq, utilizes single-cell ...
  89. [89]
    Hematopoietic Stem Cell Transplantation - StatPearls - NCBI - NIH
    Hematopoietic stem cell transplant (HPSCT), sometimes referred to as bone marrow transplant, involves administering healthy hematopoietic stem cells to patients
  90. [90]
    Hematopoietic Stem Cells - AABB
    Hematopoietic progenitor cells (HPCs) or hematopoietic stem cells (HSCs) are cells present in blood and bone marrow. HPCs are capable of forming mature ...
  91. [91]
    Hematopoietic Stem Cell Transplantation (HSCT)
    Mar 17, 2025 · Hematopoietic stem cell transplantation (HSCT) involves the intravenous infusion of hematopoietic stem cells in order to reestablish blood cell production.
  92. [92]
    The CD34+ Cell Dose Matters in Hematopoietic Stem Cell ... - NIH
    In the multivariate analysis, a CD34 cell dose of 6–7 × 106/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × ...
  93. [93]
    Engraftment - an overview | ScienceDirect Topics
    In general, WBC engraftment occurs 7 to 14 days after peripheral blood stem cell infusion, 10 to 21 days after bone marrow stem cell infusion, and 10 to 28 days ...
  94. [94]
    Stem cells from bone marrow or stem cells from peripheral blood
    Nov 7, 2024 · However, the growth of stem cells and new blood cells (known as engraftment) is slower after bone marrow transplantation than after peripheral ...<|separator|>
  95. [95]
    Stem cell homing: From physiology to therapeutics - Liesveld - 2020
    Jun 11, 2020 · Stem cell homing is a multistep endogenous physiologic process that is also used by exogenously administered hematopoietic stem and progenitor cells (HSPCs).
  96. [96]
    Hematopoietic stem and progenitor cells use podosomes to ...
    Jan 23, 2020 · Hematopoietic stem cell transplantation is used to restore hematopoiesis in patients with (hematological) malignancies and disorders after ...
  97. [97]
    Sources of Hematopoietic Stem and Progenitor Cells and Methods ...
    Hematopoietic stem cells from various graft sources are used in transplantation. •. Bone marrow stem cell grafts may be optimized by using G-CSF. •.Hspc Collection And Cellular... · G-Csf--Primed Bm Stem Cell... · Hla Haplotype Matched...
  98. [98]
    A Narrative Review of Advances in Neural Precursor Cell ...
    Dec 31, 2022 · Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function. Cell Rep.
  99. [99]
    Neural stem cell transplantation in patients with progressive multiple ...
    Jan 9, 2023 · Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection ...
  100. [100]
    The interplay of inflammation and remyelination: rethinking MS ...
    Jul 12, 2024 · Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury ...
  101. [101]
    CRISPR-edited human ES-derived oligodendrocyte progenitor cells ...
    Oct 9, 2024 · ... oligodendrocyte precursor cells may help overcome remyelination inhibitors and improve remyelination after transplantation into mouse brain.
  102. [102]
    Phloretin enhances remyelination by stimulating oligodendrocyte ...
    Nov 7, 2022 · In this study, we provide evidence that phloretin enhances remyelination in ex vivo and in vivo animal models by stimulating oligodendrocyte precursor cell ...
  103. [103]
    The Future of Regenerative Medicine: Cell Therapy Using ...
    The future of regenerative medicine: Cell therapy using pluripotent stem cells and acellular therapies based on extracellular vesicles.
  104. [104]
    Single-cell transcriptome of early hematopoiesis guides arterial ...
    Sep 3, 2021 · We performed extensive single-cell transcriptomic analyses to map fate choices and gene expression patterns during hematopoietic differentiation of hPSCs.Results · Scrna-Seq Analysis Of... · Oxidative Metabolism Is...<|separator|>
  105. [105]
    Technical Advances in Single-Cell RNA Sequencing and ... - Frontiers
    Here, we aim to review the recent technical progress and future prospects for scRNA-seq, as applied in physiological and malignant hematopoiesis.
  106. [106]
    A comprehensive single cell transcriptional landscape of human ...
    Jun 3, 2019 · Using single-cell RNA-Seq, we show that existing approaches to stratify bone marrow CD34+ cells reveal a hierarchically-structured ...
  107. [107]
    Single cell transcriptomics reveals unanticipated features of early ...
    Early hematopoietic precursors show multiple levels of molecular heterogeneity. We examined subpopulations (Supplementary Data, Supplementary Data) of the ...Cell Culture · Flow Cytometry And... · Results
  108. [108]
    An immunophenotype-coupled transcriptomic atlas of human ...
    Mar 21, 2024 · This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.
  109. [109]
    Mapping the cellular biogeography of human bone marrow niches ...
    May 6, 2024 · We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes ...
  110. [110]
    A single-cell resolution developmental atlas of hematopoietic stem ...
    Apr 6, 2021 · A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish ... Hematopoietic Stem Cells ...
  111. [111]
    and single-cell-resolved model of murine bone marrow hematopoiesis
    Jan 5, 2024 · This study models murine bone marrow hematopoiesis using a time-resolved, single-cell approach, tracking HSC differentiation over time, and ...
  112. [112]
    The Atlas of Human Hematopoietic Stem Cell Development - UCLA
    The single cell Atlas of Human Hematopoietic Stem Cell Development provides access to gene expression profiles of human HSCs throughout ontogeny.
  113. [113]
    A single-cell resolution map of mouse hematopoietic stem and ... - NIH
    An expression map of HSPC differentiation from single-cell RNA sequencing of HSPCs provides insights into blood stem cell differentiation. A user-friendly Web ...
  114. [114]
    Counting blood precursors - PMC
    Jul 17, 2024 · A new mathematical model can estimate the number of precursor cells that contribute to regenerating blood cells in mice.
  115. [115]
    Developmental genetics with model organisms - PMC - NIH
    Jul 18, 2022 · ... precursor cells. Although the invariance of cell divisions suggested a determination of cell fate via asymmetric cell divisions, in many ...
  116. [116]
    New Roles for Model Genetic Organisms in Understanding and ...
    Studies of stem cells in Drosophila, mouse, and other model systems have greatly advanced our understanding of their regulation within stem cell niches ...
  117. [117]
    Zebrafish as an animal model for biomedical research - Nature
    Mar 1, 2021 · ... model organisms, including rodents. This possibility has been ... precursor cells in zebrafish, which are apparent during neurogenesis ...
  118. [118]
    Continuous map of early hematopoietic stem cell differentiation ...
    Mar 7, 2025 · These experiments demonstrated increased expression levels of stemness genes, such as Thy1, HOPX, DLK1, MPL, and MLLT3 in CD273high HSPCs, while ...
  119. [119]
    Deciphering the effect of UM171 on human hematopoietic ... - Nature
    Jan 2, 2025 · We show that, in addition to its HSC self-renewing property, UM171 specifically modulates cell fate of a precursor common to erythroid, megakaryocytic, and ...Results · Um171 Enhances Hsc... · Um171 Drives Transcriptional...<|separator|>
  120. [120]
    An in vitro model of human hematopoiesis identifies a regulatory ...
    Oct 13, 2023 · An in vitro stromal cell–free model that allows concurrent study of multiple human hematopoietic lineages was identified.Results · Ahr Activation By Tcdd... · Ahr Activation Suppresses...
  121. [121]
    An In Vitro Study of Differentiation of Hematopoietic Cells to ...
    In this paper, we present an in vitro model of cell differentiation from hematopoietic stem/progenitor cells in BMMNC to endothelial linage. Given the ...2.6. Secreted Growth Factors · 3. Results · 3.5. Endocytic Capability
  122. [122]
    Modeling of human T cell development in vitro as a read-out for ...
    Oct 13, 2021 · In vitro models for T cell development include fetal thymic organ cultures (FTOCs), OP9-DLL1/4 coculture, artificial thymic organoids (ATO), ...Human T Cell Development In... · Op9-Dll1/4 Coculture Models · Artificial Thymic Organoids
  123. [123]
    In Vitro Human Haematopoietic Stem Cell Expansion and ... - MDPI
    This review discusses the in vitro culture protocols for human HSC expansion and differentiation, and summarises the key factors involved in these biological ...2.2. Small-Molecules · 5.1. Neutrophils · 6.2. T Cells
  124. [124]
    Plasticity of Adult Stem Cells - ScienceDirect.com
    Transdifferentiation describes the conversion of a cell of one tissue lineage into a cell of an entirely distinct lineage, with concomitant loss of the tissue- ...Missing: disputes | Show results with:disputes
  125. [125]
    Adult cell plasticity in vivo: de-differentiation and transdifferentiation ...
    Recent studies have highlighted the extent to which cell plasticity contributes to tissue homeostasis, findings that have implications for cell-based therapy.
  126. [126]
    Stem cell plasticity: from transdifferentiation to macrophage fusion
    Recent data, however, argue against the whole idea of stem cell 'plasticity', and bring into question the therapeutic strategies based upon this concept.
  127. [127]
    Stem cell plasticity, cell fusion, and transdifferentiation - PubMed - NIH
    This review will provide an overview of the stem cell plasticity controversy. We will examine many of the major objections that have been made to challenge the ...
  128. [128]
    Stem cell plasticity, cell fusion, and transdifferentiation
    Aug 25, 2003 · One of the most contentious issues in biology today concerns the existence of stem cell plasticity. The term “plasticity” refers to the ...Missing: disputes | Show results with:disputes
  129. [129]
    Molecular Genetic Advances in Cardiovascular Medicine | Circulation
    Despite the evidence for adult stem cell plasticity, a group of skeptics has come forward, denying the existence of the phenomenon or classifying it as a ...
  130. [130]
    The concept of stem cell plasticity or transdifferentiation ability is...
    The concept of stem cell plasticity or transdifferentiation ability is controversial, but refers to the possibility that tissue-specific (unipotent) stem cells ...<|separator|>
  131. [131]
    Insights Into the Cellular Origin of Gastric Metaplasia
    Cellular plasticity is an intriguing facet of gastroin- testinal cells. In response to injury, mature cell types can reprogram to promote tissue repair and ...
  132. [132]
    Issues in stem cell plasticity - Wiley Online Library
    The studies of Clark, Frisen and co-workers supporting the idea of broad brain cell potential were also met with great skepticism. Other scientists purified and ...<|control11|><|separator|>
  133. [133]
    Nomenclature for cellular plasticity: are the terms as ... - EMBO Press
    Sep 2, 2019 · The trouble with the term, however, is that there is no consensus regarding the extent to which a cell must exhibit progenitor or embryonic ...<|separator|>
  134. [134]
    Understanding cancer stem cells and plasticity - ScienceDirect.com
    Dedifferentiation is the mechanism by which a differentiated cell reverts to a precursor cell type with the same lineage. Ectopic transcription factors such as ...
  135. [135]
    The new stem cell biology: something for everyone - PMC
    The ability of multipotential adult stem cells to cross lineage boundaries (transdifferentiate) is currently causing heated debate in the scientific press.
  136. [136]
    The quest of cell surface markers for stem cell therapy - PMC
    Cell surface markers are cell identifiers, often proteins, used to purify specific cell types at specific stages for stem cell therapy. They are identified ...
  137. [137]
    Navigating the Adipocyte Precursor Niche - Scientific Archives
    This review delves into the current landscape of knowledge surrounding adipocyte precursors within the adipose stem cell niche.Adipocyte Precursors And... · Adipocyte Precursor... · Bmp Signaling And Adipogenic...
  138. [138]
    Advances and challenges in identifying precursors of memory CD4+ ...
    May 5, 2025 · It is challenging to identify reliable precursors of TCM cells due to the shared programs underlying differentiation of TCM and Tfh cells.
  139. [139]
    Challenges and Opportunities for Consistent Classification of ...
    In this review, we shall discuss the current understanding of human B cell heterogeneity and define major parental populations and associated subsets.
  140. [140]
    [PDF] A Case Report and Literature Review | Cureus
    Oct 16, 2024 · It represents a significant clinical challenge due to its heterogeneous mutational landscape and poor response to conventional therapies. This ...
  141. [141]
    Rapid potency assessment of autologous peripheral blood stem ...
    However, the CFU assay is technically challenging, labor-intensive and difficult to standardize and requires a delay of up to 14 days for cell growth [5]. Other ...
  142. [142]
    Current practices and prospects for standardization of the ...
    Wide acceptance of the colony-forming unit (CFU) assay as a reliable potency test for stem cell products is hindered by poor inter-laboratory ...
  143. [143]
    A robust potency assay highlights significant donor variation of ...
    Dec 1, 2015 · A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended ...
  144. [144]
    Describing the Stem Cell Potency: The Various Methods of ...
    The potency of these stem cells can be defined by using a number of functional assays along with the evaluation of various molecular markers.
  145. [145]
    Potency testing of cell and gene therapy products - Frontiers
    May 4, 2023 · In this article the challenges of potency testing are discussed together with examples of assays used for different CGTs/ATMPs and the available guidance.