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At least 631 records · Page 35Linked to original sources
PubMed2006

Transcription factor control of asymmetric cell divisions that establish the stomatal lineage.

The establishment of new cell lineages during development often requires a symmetry-breaking event. An asymmetric division in the epidermis of plants initiates a lineage that ultimately produces stomatal guard cells. Stomata are pores in the epidermis that serve as the main conduits for gas exchange between plants and the atmosphere; they are critical for photosynthesis and exert a major influence on global carbon and water cycles. Recent studies implicated intercellular signalling in preventing the inappropriate production of stomatal complexes. Genes required to make stomata, however, remained elusive. Here we report the identification of a gene, SPEECHLESS (SPCH), encoding a basic helix-loop-helix (bHLH) transcription factor that is necessary and sufficient for the asymmetric divisions that establish the stomatal lineage in Arabidopsis thaliana. We demonstrate that SPCH and two paralogues are successively required for the initiation, proliferation and terminal differentiation of cells in the stomatal lineage. The stomatal bHLHs define a molecular pathway sufficient to create one of the key cell types in plants. Similar molecules and regulatory mechanisms are used during muscle and neural development, highlighting a conserved use of closely related bHLHs for cell fate specification and differentiation.

Arabidopsis↗
PubMed2001

Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage.

The process of thymocyte development culminates in the maturation of helper (CD4+) and cytotoxic (CD8+) T cells from their common precursors, the CD4+CD8+ double-positive cells. A crucial step during lineage specification is the termination of expression of either the CD4 or the CD8 coreceptor. A silencer element within the first intron of the CD4 gene is sufficient for CD4 transcriptional repression in cells of the cytotoxic lineage, as well as in thymocytes at earlier stages of differentiation. Here we show that the function of the CD4 silencer is required only at distinct stages of development. Its deletion before the initiation of lineage specification resulted in CD4 derepression throughout thymocyte differentiation. By contrast, once cells committed to the cytotoxic CD8+ lineage, the CD4 locus remained silent through subsequent mitoses, even when the silencer element was excised. The epigenetic inheritance of the silenced CD4 locus was not affected by the inhibition of DNA methylation or histone deacetylation, and may thus involve other mechanisms that ensure a stable state of gene expression.

Animals↗
PubMed2005

Notch signaling controls the generation and differentiation of early T lineage progenitors.

Signaling by the transmembrane receptor Notch is critical for T lineage development, but progenitor subsets that first receive Notch signals have not been defined. Here we identify an immature subset of early T lineage progenitors (ETPs) in the thymus that expressed the tyrosine kinase receptor Flt3 and had preserved B lineage potential at low progenitor frequency. Notch signaling was active in ETPs and was required for generation of the ETP population. Additionally, Notch signals contributed to the subsequent differentiation of ETPs. In contrast, multipotent hematopoietic progenitors circulated in the blood even in the absence of Notch signaling, suggesting that critical Notch signals during early T lineage development are delivered early after thymic entry.

Animals↗
PubMed2000

Mixed chimerism in the B cell lineage is a rapid and sensitive indicator of minimal residual disease in bone marrow transplant recipients with pre-B cell acute lymphoblastic leukemia.

One of the major problems after allogeneic bone marrow transplantation (BMT) is a high frequency of leukemia relapse. We have prospectively studied the presence of donor- and recipient-derived chimeric cells in bone marrow recipients with pre-B cell acute lymphoblastic leukemia (pre-B-ALL). The chimeric status of BMT recipients was compared to minimal residual disease (MRD) detection by analysis of immunoglobulin heavy chain (IgH) and T cell receptor (TcR) genes. Post-transplant blood and bone marrow samples from 12 patients with pre-B-ALL were studied. Five patients showed mixed chimerism (MC) in the CD19-positive cell fraction. Four of them have relapsed to date. The remaining patient with MC in the B cell lineage was also MRD positive in the same samples. All seven patients with donor chimerism in the B cell fraction remain in clinical remission (P = 0.01). In samples from all five patients having MC in the B cell lineage, the patient-specific IgH or TcR rearrangement was also detected. In three of four patients who relapsed, MC in the B cell lineage was seen more than 2.5 months prior to morphologically verified relapse. The results of this comparison suggest that routinely performed MC analysis of the affected cell lineage may facilitate post-BMT monitoring and rapid therapeutic decisions in transplanted patients with pre-B-ALL.

Adolescent↗
PubMed2005

Circulating osteoblast-lineage cells in humans.

BACKGROUND: Although current evidence suggests that only a minuscule number of osteoblast-lineage cells are present in peripheral blood, we hypothesized that such cells circulate but that their concentration has been vastly underestimated owing to the use of assays that required adherence to plastic. We further reasoned that the concentration of these cells is elevated during times of increased bone formation, such as during pubertal growth. METHODS: We used flow cytometry with antibodies to bone-specific proteins to identify circulating osteoblast-lineage cells in 11 adolescent males and 11 adult males (mean [+/-SD] age, 14.5+/-0.7 vs. 37.7+/-7.6 years). Gene expression and in vitro and in vivo bone-forming assays were used to establish the osteoblastic lineage of sorted cells. RESULTS: Cells positive for osteocalcin and cells positive for bone-specific alkaline phosphatase were detected in the peripheral blood of adult subjects (1 to 2 percent of mononuclear cells). There were more than five times as many cells positive for osteocalcin in the circulation of adolescent boys (whose markers of bone formation were clearly increased as a result of pubertal growth) as compared with adult subjects (P<0.001). The percentage of cells positive for osteocalcin correlated with markers of bone formation. Sorted osteocalcin-positive cells expressed osteoblastic genes, formed mineralized nodules in vitro, and formed bone in an in vivo transplantation assay. Increased values were also found in three adults with recent fractures. CONCLUSIONS: Osteoblast-lineage cells circulate in physiologically significant numbers, correlate with markers of bone formation, and are markedly higher during pubertal growth; therefore, they may represent a previously unrecognized circulatory component to the process of bone formation.

Adolescent↗
PubMed2006

Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: role of the BMP-4 gene.

Previous studies showed that exposure of C3H10T1/2 stem cells to bone morphogenetic protein-4 (BMP-4) produced cells that convert into adipocytes at high frequency when treated with differentiation inducers. In the present investigation, an independent approach shows that BMP-4 is required for stable commitment of pluripotent stem cells to the adipocyte lineage. Exposure of proliferating 10T1/2 stem cells to 5-azacytidine, a potent DNA methylation inhibitor, gave rise to a subpopulation of cells that can be cloned and that have the capacity to undergo conversion into adipocytes upon treatment with terminal differentiation inducers. Detailed studies performed with a cloned committed subline, the A33 line, verified stable adipocyte lineage determination in the absence of exogenous BMP-4. Remarkably, this cell line expresses and secretes BMP-4 during proliferation in the same time window that exogenous BMP-4 must be added to naïve 10T1/2 cells to induce maximal adipocyte commitment. Furthermore, exposure of A33 cells to noggin, a naturally occurring BMP-4-binding antagonist, during this critical time window blocks subsequent differentiation. The role of BMP-4 in adipocyte lineage commitment is further strengthened by gene expression profiling of proliferating 10T1/2 stem cells and A33 preadipocytes. These findings revealed changes in the molecular circuitry, specifically coordinated changes in the expression of members of the BMP-4 signaling pathway, that distinguish A33 preadipocytes from uncommitted parental 10T1/2 stem cells. Together, these studies provide compelling evidence for the participation of BMP-4 in adipocyte lineage determination.

Adipocytes↗
PubMed1997

Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice.

The Paneth cell lineage is one of four epithelial lineages derived from the adult mouse small intestine's multipotent stem cell. Mature Paneth cells secrete antimicrobial peptides (cryptdins), growth factors, as well as two gene products, a secreted phospholipase A2 and matrilysin, that has been implicated as modifiers of adenoma formation in mice containing a mutation in the tumor suppressor Apc. Immature Paneth cells are located just above and below the cell layer, in intestinal crypts, that has been proposed to contain the multipotent stem cell. Paneth cells differentiate during a downward migration to the crypt base. The location and direction of Paneth cell migration, their high density and long residency time at the crypt base, and the nature of their secreted gene products, suggest that they may influence the structure and/or function of the stem cell niche. Paneth cell ablation can therefore be viewed as an experimental manipulation of the cellular microenvironment that purportedly contains the stem cell and its immediate descendants. Two types of ablation experiments were performed in transgenic mice. Nucleotides -6500 to +34 of the mouse cryptdin-2 gene (CR2) were used to express an attenuated diphtheria toxin A fragment. Light and electron microscopic immunohistochemical analyses of several pedigrees of postnatal day 28 to 180 animals established that ablation of Paneth cells is accompanied by an increase in the proportion of undifferentiated crypt base columnar cells. These cells normally co-exist with Paneth cells. The ablation does not produce a detectable effect on the proliferation or terminal differentiation programs of the other three lineages or on host-microbial interactions. The last conclusion is based on the ability of crypts to remain free of microbes detectable by Gram and Warthin-Starry stains and by retention of the normal crypt-villus distribution of components of the diffuse gut-associated lymphoid tissue. CR2-directed expression of simian virus 40 large T antigen also results in a loss of mature Paneth cells but produces a marked amplification of crypt cells having a morphology intermediate between Paneth and granule goblet cells. EM immunohistochemical analyses suggest that intermediate cells can differentiate to mature goblet cells but not to Paneth cells, as they migrate up the crypt-villus axis. Our findings suggest that (i) stemness in the crypt is not defined by instructive interactions involving the Paneth cell; (ii) expressing a Paneth cell fate may require that precursors migrate to the crypt base; (iii) antimicrobial factors produced by Paneth cells are not required to prevent colonization of small intestinal crypts; and (iv) this lineage does not function to maintain the asymmetric crypt-villus distribution of components of the diffuse gut-associated lymphoid tissue.

Animals↗
PubMed2003

Lineage-specific chimaerism quantification after T-cell depleted peripheral blood stem cell transplantation.

Patients that receive a T-cell depleted (TCD) hematopoietic stem cell transplantation (SCT) show higher risk of graft failure/rejection and of disease relapse than those that receive unmanipulated grafts. The purpose of the present investigation was to analyze the usefulness of chimaerism quantification in bone marrow (BM), peripheral blood (PB), and leukocyte lineages such as T lymphocytes (CD3+,both CD4+ and CD8+), B lymphocytes (CD19+) and myeloid cells (CD15+), for the early detection of graft failure/rejection episodes and disease relapse after TCD-PBSCT. Two of the ten (2/10) patients included in the study showed stable complete chimaerism (CC). The other 8/10 patients showed decreasing mixed chimaerism (MC) and 7 of them had either graft failure (n = 1)/rejection (n = 3) or disease relapse (n = 3). In two patients relapsed from chronic myeloid leukemia, MC was observed in BM and PB, with higher percentages of autologous cells in BM, as well as in leukocyte lineages, with higher percentages of recipient cells in the myeloid lineage than in lymphocytes. Combined analysis of chimaerism and minimal residual disease allowed early diagnosis of relapse and successful rescue therapy with donor leukocyte infusions (DLI), before the onset of hematological relapse. Chimaerism analysis allowed early diagnosis of incipient graft rejection in 3 patients. These patients showed MC both in BM and PB, with greater percentages of recipient cells in PB. Analysis of leukocyte lineages showed higher percentages of autologous cells in T lymphocytes (mainly CD8+) than in B or myeloid cells. Two of these patients were successfully treated with DLI and recovered normal PB counts and BM cellularity, as well as CC. The graft versus recipient hemopoiesis effect harbored by the donor immunocompetent cells infused seems useful forthe treatment of graft rejection, provided that an early diagnosis is made.

Adult↗
PubMed2006

Acute leukemia of dendritic cell lineage in childhood: incidence, biological characteristics and outcome.

CD4+ CD56+ malignancies have only recently been related to dendritic cell (DC) lineage. The few cases described, mostly adults and elderly, typically present with cutaneous lesions, followed by disseminated tumor localizations within a few months, with a generally very aggressive course and fatal outcome, despite the different therapeutic approaches employing chemotherapy and/or radiotherapy. Considering that leukemias in childhood and in adults are different diseases, we describe three pediatric cases to help compare the biological characteristics, immunophenotype, clinical features, treatment response and incidence of this disease in both age groups. From a total 1363 new patients with acute leukemia (AL), we report three cases with blasts of French - American - British L2 morphology, an absence of the most specific markers for myeloid, T or B lineage and lacking CD34, which led us to evaluate the blasts with an extensive panel of antibodies, including those related to the other putative pathways of lymphoid differentation: natural killer and DC. The cells expressed CD4, CD56, HLA-DR, BDCA-2 and BDCA-4. None of our cases presented with skin involvement. All three children showed good response to acute lymphoblastic leukemia (ALL) protocols, achieving complete remission even when one of the patients relapsed and received an allogeneic transplant. These findings, in spite of the small number of patients, suggest that the clinical course in children might be less aggressive, and that regular ALL protocols would be effective. We emphasize the importance of including antibodies for DC lineage in cases of CD34(-) unclassifiable AL to further characterize these rare cases (0.22%), considering that the tumor cell affiliation to DC lineage relies exclusively on immunophenotypic criteria.

Adolescent↗
PubMed2005

Influences on neural lineage and mode of division in the zebrafish retina in vivo.

Cell determination in the retina has been under intense investigation since the discovery that retinal progenitors generate clones of apparently random composition (Price, J., D. Turner, and C. Cepko. 1987. Proc. Natl. Acad. Sci. USA. 84:156-160; Holt, C.E., T.W. Bertsch, H.M. Ellis, and W.A. Harris. 1988. Neuron. 1:15-26; Wetts, R., and S.E. Fraser. 1988. Science. 239:1142-1145). Examination of fixed tissue, however, sheds little light on lineage patterns or on the relationship between the orientation of division and cell fate. In this study, three-dimensional time-lapse analyses were used to trace lineages of retinal progenitors expressing green fluorescent protein under the control of the ath5 promoter. Surprisingly, these cells divide just once along the circumferential axis to produce two postmitotic daughters, one of which becomes a retinal ganglion cell (RGC). Interestingly, when these same progenitors are transplanted into a mutant environment lacking RGCs, they often divide along the central-peripheral axis and produce two RGCs. This study provides the first insight into reproducible lineage patterns of retinal progenitors in vivo and the first evidence that environmental signals influence the orientation of cell division and the lineage of neural progenitors.

Animals↗
PubMed1997

Commitment of immature CD4+8+ thymocytes to the CD4 lineage requires CD3 signaling but does not require expression of clonotypic T cell receptor (TCR) chains.

As a consequence of positive selection in the thymus, immature CD4(+)8(+) double-positive, [DP] thymocytes selectively terminate synthesis of one coreceptor molecule and, as a result, differentiate into either CD4(+) or CD8(+) T cells. The decision by individual DP thymocytes to terminate synthesis of one or the other coreceptor molecule is referred to as lineage commitment. Previously, we reported that the intrathymic signals that induced commitment to the CD4 versus CD8 T cell lineages were markedly asymmetric. Notably, CD8 commitment appeared to require lineage-specific signals, whereas CD4 commitment appeared to occur in the absence of lineage-specific signals by default. Consequently, it was unclear whether CD4 commitment, as revealed by selective termination of CD8 coreceptor synthesis, occurred in all DP thymocytes, or whether CD4 commitment occurred only in T cell receptor (TCR)-CD3-signaled DP thymocytes. Here, we report that selective termination of CD8 coreceptor synthesis does not occur in DP thymocytes spontaneously. Rather, CD4 commitment in DP thymocytes requires signals transduced by either CD3 or zeta chains, which can signal CD4 commitment even in the absence of clonotypic TCR chains.

Animals↗
PubMed2001

Autonomous maturation of alpha/beta T lineage cells in the absence of COOH-terminal Src kinase (Csk).

The deletion of COOH-terminal Src kinase (Csk), a negative regulator of Src family protein tyrosine kinases (PTKs), in immature thymocytes results in the development of alpha/beta T lineage cells in T cell receptor (TCR) beta-deficient or recombination activating gene (rag)-1-deficient mice. The function of Csk as a repressor of Lck and Fyn activity suggests activation of these PTKs is solely responsible for the phenotype observed in csk-deficient T lineage cells. We provide genetic evidence for this notion as alpha/beta T cell development is blocked in lck(-/)-fyn(-/)- csk-deficient mice. It remains unclear whether activation of Lck and Fyn in the absence of Csk uncouples alpha/beta T cell development entirely from engagement of surface-expressed receptors. We show that in mice expressing the alpha/beta TCR on csk-deficient thymocytes, positive selection is biased towards the CD4 lineage and does not require the presence of major histocompatibility complex (MHC) class I and II. Furthermore, the introduction of an MHC class I-restricted transgenic TCR into a csk-deficient background results in the development of mainly CD4 T cells carrying the transgenic TCR both in selecting and nonselecting MHC background. Thus, TCR-MHC interactions have no impact on positive selection and commitment to the CD4 lineage in the absence of Csk. However, TCR-mediated negative selection of csk-deficient, TCR transgenic cells is normal. These data suggest a differential involvement of the Csk-mediated regulation of Src family PTKs in positive and negative selection of developing thymocytes.

Animals↗
PubMed2003

Enforced granulocyte/macrophage colony-stimulating factor signals do not support lymphopoiesis, but instruct lymphoid to myelomonocytic lineage conversion.

We evaluated the effects of ectopic granulocyte/macrophage colony-stimulating factor (GM-CSF) signals on hematopoietic commitment and differentiation. Lineage-restricted progenitors purified from mice with the ubiquitous transgenic human GM-CSF receptor (hGM-CSFR) were used for the analysis. In cultures with hGM-CSF alone, hGM-CSFR-expressing (hGM-CSFR+) granulocyte/monocyte progenitors (GMPs) and megakaryocyte/erythrocyte progenitors (MEPs) exclusively gave rise to granulocyte/monocyte (GM) and megakaryocyte/erythroid (MegE) colonies, respectively, providing formal proof that GM-CSF signals support the GM and MegE lineage differentiation without affecting the physiological myeloid fate. hGM-CSFR transgenic mice were crossed with mice deficient in interleukin (IL)-7, an essential cytokine for T and B cell development. Administration of hGM-CSF in these mice could not restore T or B lymphopoiesis, indicating that enforced GM-CSF signals cannot substitute for IL-7 to promote lymphopoiesis. Strikingly, >50% hGM-CSFR+ common lymphoid progenitors (CLPs) and >20% hGM-CSFR+ pro-T cells gave rise to granulocyte, monocyte, and/or myeloid dendritic cells, but not MegE lineage cells in the presence of hGM-CSF. Injection of hGM-CSF into mice transplanted with hGM-CSFR+ CLPs blocked their lymphoid differentiation, but induced development of GM cells in vivo. Thus, hGM-CSF transduces permissive signals for myeloerythroid differentiation, whereas it transmits potent instructive signals for the GM differentiation to CLPs and early T cell progenitors. These data suggest that a majority of CLPs and a fraction of pro-T cells possess plasticity for myelomonocytic differentiation that can be activated by ectopic GM-CSF signals, supporting the hypothesis that the down-regulation of GM-CSFR is a critical event in producing cells with a lymphoid-restricted lineage potential.

Animals↗
PubMed2004

Centromeric repositioning of coreceptor loci predicts their stable silencing and the CD4/CD8 lineage choice.

The differentiation of CD4(+) CD8(+) double positive (DP) thymocytes requires the irreversible choice between two alternative lineages, distinguished by the mutually exclusive expression of either CD4 or CD8. Differentiating DP cells transiently down-regulate both CD4 and CD8, and this has complicated the debate whether the mechanism of CD4/CD8 lineage choice is instructive, stochastic/selective, or more complex in nature. Using fluorescence in situ hybridization, we show that the stable silencing of coreceptor loci, and ultimately lineage choice, is predicted by the spatial repositioning of coreceptor alleles to centromeric heterochromatin domains. These data provide evidence that lineage-specific developmental programs are established early during the transition from the DP to the single positive stage.

Alleles↗
PubMed2005

An antagonist peptide mediates positive selection and CD4 lineage commitment of MHC class II-restricted T cells in the absence of CD4.

The CD4 coreceptor works together with the T cell receptor (TCR) to deliver signals to the developing thymocyte, yet its specific contribution to positive selection and CD4 lineage commitment remains unclear. To resolve this, we used N3.L2 TCR transgenic, RAG-, and CD4-deficient mice, which are severely impaired in positive selection, and asked whether altered peptide ligands can replace CD4 function in vivo. Remarkably, in the presence of antagonist ligands that normally deleted CD4+ T cells in wild-type mice, we induced positive selection of functional CD4 lineage T cells in mice deficient in CD4. We show that the kinetic threshold for positive and negative selection was lowered in the absence of CD4, with no evident skewing toward the CD8 lineage with weaker ligands. These results suggest that CD4 is dispensable as long as the affinity threshold for positive selection is sustained, and strongly argue that CD4 does not deliver a unique instructional signal for lineage commitment.

Amino Acid Sequence↗
PubMed2005

Identification of eosinophil lineage-committed progenitors in the murine bone marrow.

Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Ralpha(+)CD34(+)c-Kit(lo) phenotype. Normal bone marrow cells also contained IL-5Ralpha(+)CD34(+)c-Kit(lo) EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Ralpha in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Ralpha(+) GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Ralpha might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils.

Animals↗
PubMed2006

E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment.

The helix-loop-helix protein, E47, is essential for both B- and T-lineage development. Here we demonstrate that in vitro E47 and Notch signaling act in concert to promote T cell development from fetal hematopoietic progenitors and to restrain development into the natural killer and myeloid cell lineages. The expression of an ensemble of genes associated with Notch signaling is activated by E47, and additionally, Notch signaling and E47 act in parallel pathways to induce a T lineage-specific program of gene expression. Enforced expression of the intracellular domain of Notch rescues the developmental arrest at the T cell commitment stage in E2A-deficient fetal thymocytes. Finally, we demonstrate that regulation of Hes1 expression by Notch signaling and E47 is strikingly similar to that observed during Drosophila melanogaster sensory development. Based on these observations, we propose that in developing fetal thymocytes E47 acts to induce the expression of an ensemble of genes involved in Notch signaling, and that subsequently E47 acts in parallel with Notch signaling to promote T-lineage maturation.

Animals↗
PubMed1997

Lineage commitment of HLA-DR/CD38-defined progenitor cell subpopulations in bone marrow and mobilized peripheral blood assessed by four-color immunofluorescence.

We used four-color fluorescence analysis to compare lineage antigen expression in relationship to CD38 and HLA-DR on CD34+ progenitor cells in adult human bone marrow and mobilized peripheral blood. Each of four progenitor cell subpopulations defined by HLA-DR and CD38 intensity (CD38-/HLA-DR-, CD38-/HLA-DR+, CD38+/HLA-DR+, and CD38+/HLA-DR-) were present in both progenitor cell sources in similar ratios. The most prevalent subpopulation consisted of cells that expressed both CD38 and HLA-DR. Virtually all progenitor cells that lacked CD38 also lacked lineage antigens regardless of their HLA-DR expression. In contrast, the majority of the cells within both CD38+ progenitor cell subpopulations possessed either lineage antigens or the proliferation-associated antigen, CD71. Furthermore, CD71 was expressed on three times the number of CD38+/HLA-DR- cells when compared with the CD38-/HLA-DR- subpopulation. Within CD34+ progenitor cell subpopulations defined by the expression of CD38 and HLA-DR, the CD38+/HLA-DR- component appears to be the most mature, based on the expression of CD71 and various lineage-associated antigens, including representative markers characterizing early lymphoid, myeloid, and erythroid precursors. Thus, selection of the most immature CD34+ progenitor cells based solely on the lack of HLA-DR expression results in isolation of two distinct cell populations with markedly different maturation status and resultant growth characteristics.

ADP-ribosyl Cyclase↗