Definitive Hematopoiesis In the Mammalian Embryo Prior to HSC Formation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1599-1599
Author(s):  
Kathleen E McGrath ◽  
Jenna M Frame ◽  
Anne Koniski ◽  
Paul D Kingsley ◽  
James Palis
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Differentiation ◽  
Blood Cells ◽  
Fetal Liver ◽  
Yolk Sac ◽  
Es Cell ◽  
Hematopoietic Progenitors ◽  
Adult Bone ◽  
Myeloid Progenitors

Abstract Abstract 1599 The ontogeny of hematopoiesis in mammalian embryos is complicated by the requirement for functional blood cells prior to the emergence of hematopoietic stem cells or the bone marrow microenvironment. In the murine embryo, transplantable HSC are first evident at embryonic day (E) 10.5 and the first few HSC are found in the fetal liver hematopoietic environment by E12.5. However, two overlapping waves of hematopoietic potential arise in the yolk sac before E10.5. The first “primitive” wave produces progenitors from E7.25 to E8.5 with primitive erythroid, megakaryocyte and macrophage potentials. The resulting primitive erythroid cells mature within the circulation and support embryonic growth past E9.5. At E8.5, a second wave of hematopoiesis begins in the yolk sac and generates definitive erythroid and multiple myeloid progenitors that are the proposed source of the hematopoietic progenitors seeding the fetal liver before HSC colonization. We have identified a cell population displaying a unique cell surface immunophenotype in the E9.5 yolk sac that contains the potential to form definitive erythroid cells, megakaryocytes, macrophages and all forms of granulocytes within days of in vitro culture. Furthermore, all definitive hematopoietic colony-forming cells (BFU-E, CFC-myeloid and HPP-CFC) in the E9.5 yolk sac have this immunophenotype. These erythro-myeloid progenitors (EMP) are lineage-negative and co-express ckit, CD41, CD16/32 and Endoglin. Interestingly, this is not an immunophenotype evident in the adult bone marrow. Other markers that have been associated with HSC formation (AA4.1, ScaI) or with lymphoid potential (IL7R, Flt3) are not present on these cells at E9.5. Consistent with the lack of lymphoid markers, we also do not observe short-term development of B-cells (CD19+B220+ expressing Rag2 RNA) in cultures of the E9.5 sorted EMP, while bone marrow Lin-/ckit+/ScaI- cells do form B-cells under the same conditions. Clonal analysis of sorted EMP cells revealed single cells with both erythroid and granulocyte potential, similar to the common myeloid progenitors in adult bone marrow. Though these EMP are enriched at E9.5 in the yolk sac, they are also found at low levels in the fetal blood, embryo proper and placenta, consistent with their entrance into the circulation. By E10.5, EMP were most highly enriched in the newly formed fetal liver. Additionally by E12.5, a time when the first few HSCs are detected in the fetal liver, we find active erythropoiesis and granulopoiesis in the liver and the first definitive red blood cells and neutrophils in the bloodstream. Therefore, we believe the yolk sac definitive progenitors' fate is to populate the fetal liver and thus provide the first definitive erythrocytes and granulocytes for the embryo. The differentiation of embryonic stem cells (ES) and induced pluripotent stem cells (iPS) cells into mature cells types offers the hope of cell-based therapies. Analysis of differentiating murine ES cells reveals overlapping waves of primitive and definitive hematopoietic colony forming potential. We demonstrate the appearance of an EMP-like (ckit+/CD41+/FcGR+) population coincident with the emergence of definitive hematopoietic progenitors during murine ES cell differentiation as embryoid bodies. We have confirmed with colony forming assays that definitive hematopoietic potential is associated with this immunophenotypic group. Our studies support the concept that blood cell emergence during ES cell differentiation closely mimics pre-HSC hematopoiesis in the yolk sac. Disclosures: No relevant conflicts of interest to declare.

Efficient Expression of a Kit/GFP Transgene in Hematopoietic Stem Cells of Mouse Fetal Liver and Bone Marrow.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4159-4159
Author(s):  
Francesco Cerisoli ◽  
Letizia Cassinelli ◽  
Giuseppe Lamorte ◽  
Stefania Citterio ◽  
Maria Cristina Magli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Fetal Liver ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem ◽  
Adult Bone Marrow ◽  
Gfp Fluorescence ◽  
Adult Bone

Abstract The hierarchy of transcription factors and signalling molecules involved in hematopoietic development has been dissected through transgenic and knock-out experiments, leading to the identification of several important genes. Less well known are the networks of transcription factors which regulate the activities of the main genes identified. Kit, encoding the membrane receptor of Stem Cell Factor (SCF), is a critical molecule for Hematopoietic Stem Cells (HSC) and some early progenitors, in which it is expressed. In a previous work (Cairns et al., Blood102, 3954;2003), we used mouse lines expressing transgenic Green Fluorescent Protein (GFP) under the control of Kit regulatory elements to investigate Kit regulation in different cell systems such as the hematopoietic and germ cell lineages. We generated a mouse Kit transgene capable of efficiently driving GFP expression both in PGC and in hematopoietic progenitors, such as CFU-Mix and BFU-Es. In the present work, we evaluated the functional efficiency of the same transgene also in HSC residing in the Fetal Liver (FL) and adult Bone Marrow (BM). To test if the construct is expressed in HSC, we transplanted FL or BM cells, fractionated on the basis of Kit expression and the level of GFP fluorescence, into irradiated non-transgenic mice. At the same time, the proportion of hematopoietic progenitors in the various fractions was assessed by in vitro colony assays. Following long term hematological reconstitution, the contribution of transplanted GFP cells was evaluated by the proportion of fluorescent mixed colonies in colture as well as by the proportion of fluorescent bone marrow cells, as assessed by FACS analysis. Long term reconstitution was confirmed by secondary transplants. Results show that the repopulating cells derived from fetal liver and adult bone marrow reside in a fraction of Kit+ cells with intermediate GFP fluorescence level, whereas CFU-Mix and BFU-E are in the highly GFP fluorescent fraction. Furthermore, flow cytometry of fetal liver shows that the intermediate fluorescence fraction is highly enriched in Kit+, Sca1+, CD11b+ cells (the expected HSC immunophenotype), whereas the high fluorescence fraction contains mainly Kit+, Sca1−, CD11b− cells. Similarly, the HSC-enriched tip of the Side Population (SP) of adult bone marrow is highly enriched in Kit+, Sca1+ cells of intermediate GFP fluorescence, whereas the upper part of the SP is enriched in Kit+, Sca1− cells of high GFP fluorescence. Our results indicate that the transgene (and possibly the endogenous Kit gene as well) might be transcribed at relatively low levels in HSC versus other progenitors. Noteworthy, the same transgene is also highly expressed in PGC and in Cardiac Stem Cells (CSC) (Messina et al., Circ. Res. 95,911;2004) and in blastocyst inner mass grown in vitro, indicating that the most 5′ part of the intron (4kb), added to the otherwise inactive promoter might include sites regulating Kit expression in multiple stem cell types.

scholarly journals The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their liver adult bone marrow counterparts

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3500-3507 ◽  
Author(s):  
VI Rebel ◽  
CL Miller ◽  
CJ Eaves ◽  
PM Lansdorp
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Blood Cells ◽  
Fetal Liver ◽  
Hematopoietic Stem ◽  
Adult Bone Marrow ◽  
Significant Difference ◽  
Adult Bone ◽  
Marrow Cells

Varying, limiting numbers of unseparated or purified cells (Ly-5.1), either from 14.5-day-old fetal liver (FL) or from adult bone marrow (BM) were coinjected with 10(5) unseparated BM cells (Ly-5.2) into lethally irradiated adult C57B1/6 recipients (Ly-5.2). The kinetics of donor cell repopulation of the lymphoid and myeloid compartments by Ly- 5.1+ donor hematopoietic stem cells (ie, competitive repopulation units [CRU]) were monitored at various time points after the transplantation by Ly-5 analysis of the peripheral white blood cells (WBC). Recipients that had received on average less than 2 adult BM or FL CRU did not show a significant difference in the level of donor-reconstitution when analyzed 4 weeks after the transplantation, However, at 8 and 16 weeks, the FL recipients showed a significantly higher percentage of donor- derived nucleated peripheral blood cells than did the recipients of adult BM cells. Analysis of individual mice showed that approximately 80% of the recipients of FL CRU showed an increase in mature WBC output between 4 and 8 weeks after transplantation, whereas this occurred in less than 40% in the recipients of adult BM cells. In addition to this effect on mature cell output, the cellularity of the reconstituted BM was significantly higher in recipients of FL CRU than in recipients of adult BM CRU, even at 7 to 9 months after transplantation, which is consistent with an increased clonal expansion of FL CRU. When marrow cells from primary recipients of FL CRU were injected into secondary recipients, a significantly higher percentage of these mice showed donor-reconstitution of their lymphoid and myeloid compartments (P < .01) and to a greater extent (P < .008) as compared with mice that had received marrow cells from primary recipients of similar numbers of adult BM CRU. Taken together, these results show that individual FL CRU exhibit a greater proliferative activity in vivo than similar cells from adult BM that is accompanied by a greater production of daughter CRU.

scholarly journals The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice

Blood ◽  
2009 ◽  
Vol 113 (13) ◽  
pp. 2914-2923 ◽  
Author(s):  
Takafumi Yokota ◽  
Kenji Oritani ◽  
Stefan Butz ◽  
Koichi Kokame ◽  
Paul W. Kincade ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Fetal Liver ◽  
Microarray Technology ◽  
Hematopoietic Progenitors ◽  
Erythroid Progenitors ◽  
Hematopoietic Stem ◽  
Endothelial Antigen ◽  
Adult Bone

Abstract Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecule (ESAM) as a novel marker for murine HSCs in fetal liver. Esam was expressed at high levels within a Rag1− c-kitHi Sca1+ HSC-enriched fraction, but sharply down-regulated with activation of the Rag1 locus, a valid marker for the most primitive lymphoid progenitors in E14.5 liver. The HSC-enriched fraction could be subdivided into 2 on the basis of ESAM levels. Among endothelial antigens on hematopoietic progenitors, ESAM expression showed intimate correlation with HSC activity. The ESAMHi population was highly enriched for multipotent myeloid-erythroid progenitors and primitive progenitors with lymphopoietic activity, and exclusively reconstituted long-term lymphohematopoiesis in lethally irradiated recipients. Tie2+ c-kit+ lymphohematopoietic cells in the E9.5–10.5 aorta-gonad-mesonephros region also expressed high levels of ESAM. Furthermore, ESAM was detected on primitive hematopoietic progenitors in adult bone marrow. Interestingly, ESAM expression in the HSC-enriched fraction was up-regulated in aged mice. We conclude that ESAM marks HSC in murine fetal liver and will facilitate studies of hematopoiesis throughout life.

A comparison of murine T-cell–depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 364-371 ◽  
Author(s):  
Benny J. Chen ◽  
Xiuyu Cui ◽  
Gregory D. Sempowski ◽  
Maria E. Gooding ◽  
Congxiao Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Blood Cells ◽  
Immune Reconstitution ◽  
Full Term ◽  
Fetal Blood ◽  
Adult Bone

Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. A major area of concern for the use of cord blood transplantation is the delay in myeloid and lymphoid recovery. To directly compare myeloid and lymphoid recovery using an animal model of bone marrow and cord blood as sources of stem cells, hematopoietic engraftment and immune recovery were studied following infusion of T-cell–depleted adult bone marrow or full-term fetal blood cells, as a model of cord blood in a murine allogeneic transplantation model (C57BL/6 [H-2b] → BALB/c [H-2d]). Allogeneic full-term fetal blood has poorer radioprotective capacity but greater long-term engraftment potential on a cell-to-cell basis compared with T-cell–depleted bone marrow. Allogeneic full-term fetal blood recipients had decreased absolute numbers of T, B, and dendritic cells compared with bone marrow recipients. Splenic T cells in allogeneic full-term fetal blood recipients proliferated poorly, were unable to generate cytotoxic effectors against third-party alloantigens in vitro, and failed to generate alloantigen-specific cytotoxic antibodies in vivo. In addition, reconstituting T cells in fetal blood recipients had decreased mouse T-cell receptorδ single-joint excision circles compared with bone marrow recipients. At a per-cell level, B cells from fetal blood recipients did not proliferate as well as those found in bone marrow recipients. These results suggest that full-term fetal blood can engraft allogeneic hosts across the major histocompatibility barrier with slower hematopoietic engraftment and impaired immune reconstitution.

A Novel Method for Efficient Production of Multipotential Hematopoietic Progenitors from Human Embryonic Stem Cells by Co-Culture with Murine Fetal Liver-Derived Stromal Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4214-4214
Author(s):  
Feng Ma ◽  
Dan Wang ◽  
Sachiyo Hanada ◽  
Hirohide Kawasaki ◽  
Yuji Zaike ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Stromal Cells ◽  
Blood Cells ◽  
Fetal Liver ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Efficient Production ◽  
Hematopoietic Progenitors

Abstract Human embryonic stem cells provide a unique tool to study early events occurring in the development of human embryonic hematopoiesis, and their totipotent capability indicates a potent clinical application based on the cellular therapy and the evaluation of drug effects on hematopoietic and blood cells. To achieve efficient production of hematopoietic cells from human embryonic stem cells, we attempted to reproduce the circumstance surrounding embryonic hematopoietic cells in vitro. Since fetal liver is the predominant source of hematopoietic and blood cells in mammalian embryogenesis, we established stromal cells from mouse fetal liver at days 14 to 15 of gestation. In the co-culture of human embryonic stem cells with the established stromal cells, a number of hematopoietic progenitors were generated at around day 14 of co-culture, and this hematopoietic activity was highly enriched in the cobble stone-like cells under the stromal layer. Most of the cobble stone-like cells collected expressed CD34 and contained a variety of hematopoietic colony-forming cells, especially multilineage colony-forming cells, at a high frequency. The multipotential hematopoietic progenitors in the cobble stone-like cells produced all types of mature blood cells, including adult type hemoglobin-synthesizing erythrocytes and tryptase and chymase-bouble positive mast cells in the suspension cultiue with a cytokine cocktail. The developed co-culture system of human embryonic stem cells should offer a novel source for hematopoietic and blood cells applicable to cellular therapies and drug screening.

The First Trimester Human Placenta Is a Site of Primitive Red Blood Cell Maturation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2224-2224
Author(s):  
Benjamin J. Van Handel ◽  
Sacha Prashad ◽  
Andy Huang ◽  
Eija Hamalainen ◽  
Angela Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Red Blood Cells ◽  
Human Placenta ◽  
Blood Cells ◽  
Fetal Liver ◽  
First Trimester ◽  
Yolk Sac ◽  
Primitive Hematopoiesis ◽  
Placental Macrophages ◽  
Definitive Erythropoiesis

Abstract Embryonic hematopoiesis occurs in multiple anatomic sites and is generally divided into two waves, primitive and definitive. The primitive wave produces mostly red blood cells in the yolk sac, while the definitive wave generates hematopoietic stem cells (HSCs) that provide lifelong blood homeostasis. Definitive erythropoiesis, occurring first in the fetal liver and eventually the bone marrow, is an orchestrated process in which erythroblasts cluster around a central macrophage. These functional units, termed erythroblast islands, facilitate the maturation of nucleated erythroblasts to enucleated erythrocytes. It has long been thought that primitive red cells maintain their nucleus until undergoing apoptosis; however, the enucleation of primitive erythroblasts has been recently documented in mice, although the site at which this occurs is unknown. We have recently identified the placenta as a major hematopoietic organ that promotes the development of HSCs in mice; preliminary data suggests that the first trimester human placenta also supports definitive hematopoiesis. Surprisingly, our most recent findings indicate a novel, unexpected role for the human placenta in primitive hematopoiesis: the promotion of terminal maturation of primitive erythroblasts. Analysis of placental sections revealed a striking tendency of primitive red blood cells to extravasate from blood vessels in the villi and migrate out into the stroma. Furthermore, once out in the stroma, primitive erythroblasts mature: they lose expression of CD43 and enucleate. The finding that human primitive red blood cells enucleate is undocumented; interestingly, the developmental timing of erythroblast enucleation in humans parallels that in mice. At three weeks, nascent vessels in the placenta are empty, but starting at about 4 weeks, placental circulation begins and fills these vessels with large, nucleated primitive erythroblasts generated in the yolk sac. The migration of primitive erythroblasts into the stroma occurs between 4.5 and 7 weeks. Enucleation mirrors this process, with a large enrichment of enucleated cells in the stroma versus in the vessels at early developmental ages, suggesting that primitive erythroblasts enucleate in the placental stroma. This phenomenon is restricted to placental villi and does not occur in the chorionic plate. Strikingly, extravasated erythroblasts are often in close proximity to placental macrophages, reminiscent of the macrophage-erythroblast associations seen in fetal liver and bone marrow erythropoiesis at later developmental stages. Fetal liver-derived definitive erythrocytes enter circulation at around 8 weeks. After 9–10 weeks, most red blood cells can be observed in vessels, and almost all are enucleated. The concerted processes of extravasation and maturation of primitive erythroblasts in placental stroma nominate the placenta as an important site in primitive hematopoiesis. Furthermore, the association between placental macrophages and primitive erythroblasts suggests that primitive and definitive erythropoiesis share common mechanisms of terminal maturation.

Modeling CML Development and Drug Resistance Using iPSC Technology,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3767-3767
Author(s):  
Kran Suknuntha ◽  
Yuki Ishii ◽  
Kejin Hu ◽  
Jean YJ Wang ◽  
Igor Slukvin
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Stem Cell ◽  
Blood Cells ◽  
Kinase Activity ◽  
Hematopoietic Cells ◽  
Patient Specific ◽  
Hematopoietic Progenitors ◽  
Abl Kinase

Abstract Abstract 3767 Reprogramming of neoplastic cells to pluripotency provides a unique tool to personalize the exploration of tumor pathogenic mechanisms and drug resistance using iPSCs with patient-specific chromosomal abnormalities. We have developed a technology to generate transgene-free iPSCs from bone marrow and cord blood cells employing episomal vectors. Using this approach we created transgene-free iPSCs from a patient with CML in the chronic phase. CMLiPSCs showed a unique complex chromosomal translocation identified in the patinet's marrow sample while displaying typical embryonic stem cell phenotype and pluripotent differentiation potential. Importantly, these CMLiPSCs are devoid of genomic integration and expression of reprogramming factors, which are incompatible for modeling tumor development and drug response (Hu et al. Blood 117:e109). We have also shown that these CMLiPSCs contain the BCR-ABL oncogene without any detectable mutations in its kinase domain. By coculture with OP9, we generated APLNR+ mesodermal cells, MSCs, and lin-CD34+CD45+ hematopoietic progenitors from CMLiPSCs, and control BMiPSCs from a normal subject and analyzed the levels of BCR-ABL protein and tyrosine-phosphorylated (pTyr) cellular proteins in the different cell populations. The highest level of BCR-ABL protein expression was found in the in undifferentiated iPSCs, however, the overall cellular pTyr levels was lower than the control BMiPSCs, suggesting that BCR-ABL kinase activity was suppressed in the CMLiPScs. Consistent with these findings, imatinib does not inhibit the growth and survival of these CMLiPSCs. The levels of BCR-ABL protein decreased upon differentiation with a major reduction observed when cells became mesoderm. Following differentiation of CMLiPSC-derived mesoderm into the MSCs and lin-CD34+CD45+ hematopoietic progenitors, the levels of BCR-ABL protein did not change significantly, indicating that the major epigenetic regulation of BCR-ABL expression occurs during the transition to mesoderm. In spite of the decrease in BCR-ABL expression, the total pTyr levels significantly increased following transition of CMLiPSCs to mesoderm and blood cells, suggesting recovery of BCR-ABL kinase activity during differentiation. Interestingly, we found that imatinib had no effect on CFC potential of the most primitive lin-CD34+CD45+ hematopoietic progenitors derived from CMLiPSCs, while significant inhibition in hematopoietic CFC potential was observed when we used the patient's bone marrow cells. Following expansion of lin-CD34+CD45+ progenitors in serum-free medium with cytokines, we found that more differentiated hematopoietic cells became imatinib sensitive. The differential response of progenitors versus more differentiated cells to imatinib recapitulate the clinical observation that CML stem cells display innate resistance to imatinib but their differentiated progenies become sensitive to this BCR-ABL kinase inhibitor. The iPSC-based models provide several advantages for the study of CML pathogenesis. iPSCs can provide an unlimited supply of hematopoietic cells carrying patient-specific genetic abnormalities. Using well-defined temporal windows and surface markers, distinct cell subsets with tumor-initiating/tumor-propagating potential after transplantation in immunodeficient mice could be identified and used for drug screening. iPSC models make it possible to address CML stem-cell potential at various stages of differentiation for which it may be difficult to obtain samples from the patient, for example, at the hemangioblast stage. They also provide a unique opportunity to explore the interplays between epigenetics and oncogene function, as we have demonstrated using the CMLiPSCs. The major unsolved question is why CML stem cells are naturally resistant to imatinib, and this question can be addressed using the iPS system. Disclosures: Slukvin: CDI: Consultancy, Equity Ownership.

Podocalyxin is a CD34-related marker of murine hematopoietic stem cells and embryonic erythroid cells

Blood ◽  
2005 ◽  
Vol 105 (11) ◽  
pp. 4170-4178 ◽  
Author(s):  
Regis Doyonnas ◽  
Julie S. Nielsen ◽  
Shierley Chelliah ◽  
Erin Drew ◽  
Takahiko Hara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Fetal Liver ◽  
Erythroid Cells ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem ◽  
Nucleated Red Blood Cells ◽  
Erythroid Precursors ◽  
Valuable Marker

Abstract Podocalyxin/podocalyxin-like protein 1 [PCLP1]/thrombomucin/MEP21 is a CD34-related sialomucin. We have performed a detailed analysis of its expression during murine development and assessed its utility as a marker of hematopoietic stem cells (HSCs) and their more differentiated progeny. We find that podocalyxin is highly expressed by the first primitive hematopoietic progenitors and nucleated red blood cells to form in the embryonic yolk sac. Likewise, podocalyxin is expressed by definitive multilineage hematopoietic progenitors and erythroid precursors in fetal liver. The level of podocalyxin expression gradually declines with further embryo maturation and reaches near-background levels at birth. This is followed by a postnatal burst of expression that correlates with the seeding of new hematopoietic progenitors to the spleen and bone marrow. Shortly thereafter, podocalyxin expression gradually declines, and by 4 weeks postpartum it is restricted to a rare population of Sca-1+, c-kit+, lineage marker- (Lin-) cells in the bone marrow. These rare podocalyxin-expressing cells are capable of serially reconstituting myeloid and lymphoid lineages in lethally irradiated recipients, suggesting they have HSC activity. In summary, we find that podocalyxin is a marker of embryonic HSCs and erythroid cells and of adult HSCs and that it may be a valuable marker for the purification of these cells for transplantation.

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