Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Hematopoietic developmental pathways: on cellular basis

Oncogene volume 26, pages 6687–6696 (2007)Cite this article

Abstract

To elucidate the molecular mechanisms underlying normal and malignant hematopoietic development, it is critical to identify developmental intermediates for each lineage downstream of hematopoietic stem cells. Recent advances in prospective isolation of hematopoietic stem and progenitor cells, and efficient xenogeneic transplantation systems have provided a detailed developmental map in both mouse and human hematopoiesis, demonstrating that surface phenotypes of mouse stem–progenitor cells and their human counterparts are considerably different. Here, we summarize the phenotype and functional properties and their differences of hematopoietic stem and progenitor cell populations between mouse and human.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Adolfsson J, Borge OJ, Bryder D, Theilgaard-Monch K, Astrand-Grundstrom I, Sitnicka E et al. (2001). Upregulation of Flt3 expression within the bone marrow Lin(−)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 15: 659–669.

    CAS  PubMed  Google Scholar 

  • Adolfsson J, Mansson R, Buza-Vidas N, Hultquist A, Liuba K, Jensen CT et al. (2005). Identification of flt3(+) lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 121: 295–306.

    CAS  PubMed  Google Scholar 

  • Akashi K, Kondo M, von Freeden-Jeffry U, Murray R, Weissman IL . (1997). Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell 89: 1033–1041.

    CAS  PubMed  Google Scholar 

  • Akashi K, Traver D, Miyamoto T, Weissman IL . (2000). A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404: 193–197.

    CAS  PubMed  Google Scholar 

  • Akashi K, Traver D, Zon LI . (2005). The complex cartography of stem cell commitment. Cell 121: 160–162.

    CAS  PubMed  Google Scholar 

  • Allman D, Sambandam A, Kim S, Miller JP, Pagan A, Well D et al. (2003). Thymopoiesis independent of common lymphoid progenitors. Nat Immunol 4: 168–174.

    CAS  PubMed  Google Scholar 

  • Arinobu Y, Iwasaki H, Gurish MF, Mizuno S, Shigematsu H, Ozawa H et al. (2005). Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis. Proc Natl Acad Sci USA 102: 18105–18110.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arinobu Y, Mizuno S-I, Chong Y, Shigematsu H, Iino T, Iwasaki H et al. (2007). Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myelo-erythroid and myelo-lymphoid lineages. Cell Stem Cell (in press).

  • Back J, Allman D, Chan S, Kastner P . (2005). Visualizing PU.1 activity during hematopoiesis. Exp Hematol 33: 395–402.

    CAS  PubMed  Google Scholar 

  • Barabe F, Kennedy JA, Hope KJ, Dick JE . (2007). Modeling the initiation and progression of human acute leukemia in mice. Science 316: 600–604.

    CAS  PubMed  Google Scholar 

  • Baum CM, Weissman IL, Tsukamoto AS, Buckle AM, Peault B . (1992). Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci USA 89: 2804–2808.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bhandoola A, Sambandam A . (2006). From stem cell to T cell: one route or many? Nat Rev Immunol 6: 117–126.

    CAS  PubMed  Google Scholar 

  • Bonnet D, Dick JE . (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730–737.

    CAS  PubMed  Google Scholar 

  • Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG et al. (1997). A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci USA 94: 2551–2556.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Carow CE, Levenstein M, Kaufmann SH, Chen J, Amin S, Rockwell P et al. (1996). Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood 87: 1089–1096.

    CAS  PubMed  Google Scholar 

  • Castor A, Nilsson L, Astrand-Grundstrom I, Buitenhuis M, Ramirez C, Anderson K et al. (2005). Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med 11: 630–637.

    CAS  PubMed  Google Scholar 

  • Christensen JL, Weissman IL . (2001). Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc Natl Acad Sci USA 98: 14541–14546.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Corcoran AE, Riddell A, Krooshoop D, Venkitaraman AR . (1998). Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Nature 391: 904–907.

    CAS  PubMed  Google Scholar 

  • Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL . (2003). Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 17: 3029–3035.

    CAS  PubMed  PubMed Central  Google Scholar 

  • D'Amico A, Wu L . (2003). The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. J Exp Med 198: 293–303.

    CAS  PubMed  PubMed Central  Google Scholar 

  • DeKoter RP, Lee H-J, Singh H . (2002). PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors. Immunity 16: 297–309.

    CAS  PubMed  Google Scholar 

  • DeKoter RP, Walsh JC, Singh H . (1998). PU.1 regulates both cytokine-dependent proliferation and differentiation of granulocyte/macrophage progenitors. EMBO J 17: 4456–4468.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Forsberg EC, Serwold T, Kogan S, Weissman IL, Passegue E . (2006). New evidence supporting megakaryocyte–erythrocyte potential of flk2/flt3+ multipotent hematopoietic progenitors. Cell 126: 415–426.

    CAS  PubMed  Google Scholar 

  • Fujiwara Y, Browne CP, Cunniff K, Goff SC, Orkin SH . (1996). Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc Natl Acad Sci USA 93: 12355–12358.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Galy A, Travis M, Cen D, Chen B . (1995). Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity 3: 459–473.

    CAS  PubMed  Google Scholar 

  • Gilliland DG . (2002). Molecular genetics of human leukemias: new insights into therapy. Semin Hematol 39: 6–11.

    CAS  PubMed  Google Scholar 

  • Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G et al. (1997). Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 3: 1337–1345.

    CAS  PubMed  Google Scholar 

  • Gotze KS, Ramirez M, Tabor K, Small D, Matthews W, Civin CI . (1998). Flt3high and Flt3low CD34+ progenitor cells isolated from human bone marrow are functionally distinct. Blood 91: 1947–1958.

    CAS  PubMed  Google Scholar 

  • Gounari F, Aifantis I, Martin C, Fehling HJ, Hoeflinger S, Leder P et al. (2002). Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene. Nat Immunol 3: 489–496.

    CAS  PubMed  Google Scholar 

  • Graf T . (2002). Differentiation plasticity of hematopoietic cells. Blood 99: 3089–3101.

    CAS  PubMed  Google Scholar 

  • Hao QL, Zhu J, Price MA, Payne KJ, Barsky LW, Crooks GM . (2001). Identification of a novel, human multilymphoid progenitor in cord blood. Blood 97: 3683–3690.

    CAS  PubMed  Google Scholar 

  • Heyworth C, Pearson S, May G, Enver T . (2002). Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells. EMBO J 21: 3770–3781.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huntly BJ, Gilliland DG . (2005). Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 5: 311–321.

    CAS  PubMed  Google Scholar 

  • Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N et al. (2004). MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6: 587–596.

    CAS  PubMed  Google Scholar 

  • Igarashi H, Gregory SC, Yokota T, Sakaguchi N, Kincade PW . (2002). Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity 17: 117–130.

    CAS  PubMed  Google Scholar 

  • Igarashi H, Kuwata N, Kiyota K, Sumita K, Suda T, Ono S et al. (2001). Localization of recombination activating gene 1/green fluorescent protein (RAG1/GFP) expression in secondary lymphoid organs after immunization with T-dependent antigens in rag1/GFP knocking mice. Blood 97: 2680–2687.

    CAS  PubMed  Google Scholar 

  • Ikuta K, Weissman IL . (1992). Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. Proc Natl Acad Sci USA 89: 1502–1506.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ishikawa F, Livingston AG, Minamiguchi H, Wingard JR, Ogawa M . (2003). Human cord blood long-term engrafting cells are CD34+ CD38. Leukemia 17: 960–964.

    CAS  PubMed  Google Scholar 

  • Ishikawa F, Niiro H, Iino T, Yoshida S, Saito N, Onohara S et al. (2007). The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways. Blood (in press).

  • Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G et al. (2005). Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood 106: 1565–1573.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iwama A, Zhang P, Darlington GJ, McKercher SR, Maki R, Tenen DG . (1998). Use of RDA analysis of knockout mice to identify myeloid genes regulated in vivo by PU.1 and C/EBPalpha. Nucleic Acids Res 26: 3034–3043.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iwasaki H, Akashi K . (2007). Myeloid lineage commitment from the hematopoietic stem cell. Immunity 26: 726–740.

    CAS  PubMed  Google Scholar 

  • Iwasaki H, Mizuno S, Arinobu Y, Ozawa H, Mori Y, Shigematsu H et al. (2006). The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev 20: 3010–3021.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iwasaki H, Mizuno S, Wells RA, Cantor AB, Watanabe S, Akashi K . (2003). GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages. Immunity 19: 451–462.

    CAS  PubMed  Google Scholar 

  • Iwasaki H, Mizuno SI, Mayfield R, Shigematsu H, Arinobu Y, Seed B et al. (2005a). Identification of eosinophil lineage-committed progenitors in the murine bone marrow. J Exp Med 201: 1891–1897.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iwasaki H, Somoza C, Shigematsu H, Duprez EA, Iwasaki-Arai J, Mizuno S et al. (2005b). Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood 106: 1590–1600.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jaiswal S, Traver D, Miyamoto T, Akashi K, Lagasse E, Weissman IL . (2003). Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. Proc Natl Acad Sci USA 100: 10002–10007.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jordan CT . (2002). Unique molecular and cellular features of acute myelogenous leukemia stem cells. Leukemia 16: 559–562.

    CAS  PubMed  Google Scholar 

  • Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL et al. (2000). The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 14: 1777–1784.

    CAS  PubMed  Google Scholar 

  • Karsunky H, Merad M, Cozzio A, Weissman IL, Manz MG . (2003). Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J Exp Med 198: 305–313.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S et al. (1999). Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 93: 3074–3080.

    CAS  PubMed  Google Scholar 

  • Kogan SC, Brown DE, Shultz DB, Truong BT, Lallemand-Breitenbach V, Guillemin MC et al. (2001). BCL-2 cooperates with promyelocytic leukemia retinoic acid receptor alpha chimeric protein (PMLRARalpha) to block neutrophil differentiation and initiate acute leukemia. J Exp Med 193: 531–543.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kondo M, Weissman IL, Akashi K . (1997). Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91: 661–672.

    CAS  PubMed  Google Scholar 

  • Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J et al. (2006). Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442: 818–822.

    CAS  PubMed  Google Scholar 

  • Krueger A, von Boehmer H . (2007). Identification of a T lineage-committed progenitor in adult blood. Immunity 26: 105–116.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kulessa H, Frampton J, Graf T . (1995). GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev 9: 1250–1262.

    CAS  PubMed  Google Scholar 

  • Kuwata N, Igarashi H, Ohmura T, Aizawa S, Sakaguchi N . (1999). Cutting edge: absence of expression of RAG1 in peritoneal B-1 cells detected by knocking into RAG1 locus with green fluorescent protein gene. J Immunol 163: 6355–6359.

    CAS  PubMed  Google Scholar 

  • Lai AY, Kondo M . (2006). Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors. J Exp Med 203: 1867–1873.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mackarehtschian K, Hardin JD, Moore KA, Boast S, Goff SP, Lemischka IR . (1995). Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity 3: 147–161.

    CAS  PubMed  Google Scholar 

  • Manz MG, Miyamoto T, Akashi K, Weissman IL . (2002). Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci USA 99: 11872–11877.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin CH, Aifantis I, Scimone ML, von Andrian UH, Reizis B, von Boehmer H et al. (2003). Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potential. Nat Immunol 4: 866–873.

    CAS  PubMed  Google Scholar 

  • McKenna HJ, Stocking KL, Miller RE, Brasel K, De Smedt T, Maraskovsky E et al. (2000). Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95: 3489–3497.

    CAS  PubMed  Google Scholar 

  • Miyamoto T, Iwasaki H, Reizis B, Ye M, Graf T, Weissman IL et al. (2002). Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell 3: 137–147.

    CAS  PubMed  Google Scholar 

  • Miyamoto T, Weissman IL, Akashi K . (2000). AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 97: 7521–7526.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL . (1997). Identification of a lineage of multipotent hematopoietic progenitors. Development 124: 1929–1939.

    CAS  PubMed  Google Scholar 

  • Morrison SJ, Weissman IL . (1994). The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1: 661–673.

    CAS  PubMed  Google Scholar 

  • Na Nakorn T, Traver D, Weissman IL, Akashi K . (2002). Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S. J Clin Invest 109: 1579–1585.

    PubMed  PubMed Central  Google Scholar 

  • Nerlov C, Graf T . (1998). PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev 12: 2403–2412.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nerlov C, Querfurth E, Kulessa H, Graf T . (2000). GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription. Blood 95: 2543–2551.

    CAS  PubMed  Google Scholar 

  • Okuno Y, Iwasaki H, Huettner CS, Radomska HS, Gonzalez DA, Tenen DG et al. (2002). Differential regulation of the human and murine CD34 genes in hematopoietic stem cells. Proc Natl Acad Sci USA 99: 6246–6251.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Osawa M, Hanada K, Hamada H, Nakauchi H . (1996). Long-term lymphohematopoietic reconstitution by a single CD34- low/negative hematopoietic stem cell. Science 273: 242–245.

    CAS  PubMed  Google Scholar 

  • Passegue E, Jamieson CH, Ailles LE, Weissman IL . (2003). Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci USA 100 (Suppl 1): 11842–11849.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perry SS, Welner RS, Kouro T, Kincade PW, Sun XH . (2006). Primitive lymphoid progenitors in bone marrow with T lineage reconstituting potential. J Immunol 177: 2880–2887.

    CAS  PubMed  Google Scholar 

  • Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC et al. (1994). Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180: 1955–1960.

    CAS  PubMed  Google Scholar 

  • Puel A, Ziegler SF, Buckley RH, Leonard WJ . (1998). Defective IL7R expression in T(−)B(+)NK(+) severe combined immunodeficiency. Nat Genet 20: 394–397.

    CAS  PubMed  Google Scholar 

  • Randall TD, Lund FE, Howard MC, Weissman IL . (1996). Expression of murine CD38 defines a population of long-term reconstituting hematopoietic stem cells. Blood 87: 4057–4067.

    CAS  PubMed  Google Scholar 

  • Rappold I, Ziegler BL, Kohler I, Marchetto S, Rosnet O, Birnbaum D et al. (1997). Functional and phenotypic characterization of cord blood and bone marrow subsets expressing FLT3 (CD135) receptor tyrosine kinase. Blood 90: 111–125.

    CAS  PubMed  Google Scholar 

  • Rekhtman N, Radparvar F, Evans T, Skoultchi AI . (1999). Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Genes Dev 13: 1398–1411.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rosnet O, Buhring HJ, Marchetto S, Rappold I, Lavagna C, Sainty D et al. (1996). Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia 10: 238–248.

    CAS  PubMed  Google Scholar 

  • Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C et al. (2002). Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 100: 59–66.

    CAS  PubMed  Google Scholar 

  • Schwarz BA, Bhandoola A . (2004). Circulating hematopoietic progenitors with T lineage potential. Nat Immunol 5: 953–960.

    CAS  PubMed  Google Scholar 

  • Seshasayee D, Gaines P, Wojchowski DM . (1998). GATA-1 dominantly activates a program of erythroid gene expression in factor-dependent myeloid FDCW2 cells. Mol Cell Biol 18: 3278–3288.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sitnicka E, Bryder D, Theilgaard-Monch K, Buza-Vidas N, Adolfsson J, Jacobsen SE . (2002). Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool. Immunity 17: 463–472.

    CAS  PubMed  Google Scholar 

  • Sitnicka E, Buza-Vidas N, Larsson S, Nygren JM, Liuba K, Jacobsen SE . (2003). Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells. Blood 102: 881–886.

    CAS  PubMed  Google Scholar 

  • So CW, Karsunky H, Passegue E, Cozzio A, Weissman IL, Cleary ML . (2003). MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell 3: 161–171.

    CAS  PubMed  Google Scholar 

  • Spangrude GJ, Heimfeld S, Weissman IL . (1988). Purification and characterization of mouse hematopoietic stem cells. Science 241: 58–62.

    CAS  PubMed  Google Scholar 

  • Stirewalt DL, Radich JP . (2003). The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 3: 650–665.

    CAS  PubMed  Google Scholar 

  • Terstappen LW, Huang S, Safford M, Lansdorp PM, Loken MR . (1991). Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. Blood 77: 1218–1227.

    CAS  PubMed  Google Scholar 

  • Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U et al. (2002). Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99: 4326–4335.

    CAS  PubMed  Google Scholar 

  • Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A et al. (2004). Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304: 104–107.

    CAS  PubMed  Google Scholar 

  • Umland O, Mwangi WN, Anderson BM, Walker JC, Petrie HT . (2007). The blood contains multiple distinct progenitor populations with clonogenic B and T lineage potential. J Immunol 178: 4147–4152.

    CAS  PubMed  Google Scholar 

  • von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R . (1995). Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 181: 1519–1526.

    CAS  PubMed  Google Scholar 

  • Wagers AJ, Sherwood RI, Christensen JL, Weissman IL . (2002). Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297: 2256–2259.

    CAS  PubMed  Google Scholar 

  • Walsh JC, DeKoter RP, Lee HJ, Smith ED, Lancki DW, Gurish MF et al. (2002). Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates. Immunity 17: 665–676.

    CAS  PubMed  Google Scholar 

  • Wang J, Iwasaki H, Krivtsov A, Febbo PG, Thorner AR, Ernst P et al. (2005). Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J 24: 368–381.

    PubMed  PubMed Central  Google Scholar 

  • Ye M, Iwasaki H, Laiosa CV, Stadtfeld M, Xie H, Heck S et al. (2003). Hematopoietic stem cells expressing the myeloid lysozyme gene retain long-term, multilineage repopulation potential. Immunity 19: 689–699.

    CAS  PubMed  Google Scholar 

  • Yuan Y, Zhou L, Miyamoto T, Iwasaki H, Harakawa N, Hetherington CJ et al. (2001). AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc Natl Acad Sci USA 98: 10398–10403.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang DE, Hohaus S, Voso MT, Chen HM, Smith LT, Hetherington CJ et al. (1996). Function of PU.1 (Spi-1), C/EBP, and AML1 in early myelopoiesis: regulation of multiple myeloid CSF receptor promoters. Curr Top Microbiol Immunol 211: 137–147.

    CAS  PubMed  Google Scholar 

  • Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS et al. (1999). Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc Natl Acad Sci USA 96: 8705–8710.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang P, Zhang X, Iwama A, Yu C, Smith KA, Mueller BU et al. (2000). PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding. Blood 96: 2641–2648.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan

    H Iwasaki & K Akashi

  2. Department of Cancer Immunology and AIDS, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, USA

    K Akashi

Authors
  1. H Iwasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Akashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Akashi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iwasaki, H., Akashi, K. Hematopoietic developmental pathways: on cellular basis. Oncogene 26, 6687–6696 (2007). https://doi.org/10.1038/sj.onc.1210754

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210754

Keywords

This article is cited by

Search

Advanced search

Quick links