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 Article
  • Published:

Diversification of haematopoietic stem cells to specific lineages

Nature Reviews Genetics volume 1, pages 57–64 (2000)Cite this article

Abstract

Diverse types of blood cell (lineages) are produced from rare haematopoietic stem cells that reside in the bone marrow. This process, known as haematopoiesis, provides a valuable model for examining how genetic programs are established and executed in vertebrates, and also how homeostasis of blood formation is altered in leukaemias. So, how does an apparently small group of critical lineage-restricted nuclear regulatory factors specify the diversity of haematopoietic cells? Recent findings not only indicate how this may be achieved but also show the extraordinary plasticity of tissue stem cells in vivo.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1: Schematic view of adult haematopoiesis.
Figure 2: Proposed interactions between GATA-1, FOG-1 and PU.1, and their respective effects on gene regulation.
Figure 3: Regulatory interactions of key lineage-specific factors in cell type specification.

Similar content being viewed by others

References

  1. Weissman, I. L. Translating stem and progenitor cell biology to the clinic: barriers and opportunities . Science 287, 1442–1446 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Orkin, S. H. Development of the hematopoietic system. Curr. Opin. Genet. Dev . 6, 597–602 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  3. Dzierzak, E. & Medvinsky, A. Mouse embryonic hematopoiesis . Trends Genet. 11, 359– 366 (1995).

    Article  CAS  PubMed  Google Scholar 

  4. Moore, M. S. A. & Metcalf, D. Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo. Br. J. Haematol. 18, 279–296 ( 1970).

    Article  CAS  PubMed  Google Scholar 

  5. Medvinsky, A. L., Samoylina, N. L., Muller, A. M. & Dzierzak, E. A. An early pre-liver intraembryonic source of CFU-S in the developing mouse . Nature 364, 64–66 (1993).This manuscript provides evidence that intraembryonic HSCs are present in the mouse before the time at which they are detected in the yolk sac, using transplantation into irradiated adult mice as the test system.

    Article  CAS  PubMed  Google Scholar 

  6. Medvinsky, A. & Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86, 897 –906 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. Cumano, A., Dieterlen-Lievre, F. & Godin, I. Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 86, 907–916 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Cumano, A., Dieterlen-Lievre, F. & Godin, I. The splanchnopleura/AGM region is the prime site for the generation of multipotent hemopoietic precursors, in the mouse embryo . Vaccine 18, 1621–1623 (2000).

    Article  CAS  PubMed  Google Scholar 

  9. Godin, I., Dieterlen-Lievre, F. & Cumano, A. Emergence of multipotent hemopoietic cells in the yolk sac and paraaortic splanchnopleura in mouse embryos, beginning at 8. 5 days postcoitus. Proc. Natl Acad. Sci. USA 92, 773–777 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yoder, M. C. et al. Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac. Immunity 7, 335–344 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Yoder, M. C. & Hiatt, K. Murine yolk sac and bone marrow hematopoietic cells with high proliferative potential display different capacities for producing colony-forming cells ex vivo. J. Hematother. Stem Cell Res. 8, 421–430 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Pardanaud, L., Yassine, F. & Dieterlen-Lievre, F. Relationship between vasculogenesis, angiogenesis, and haemopoiesis during avian ontogeny. Development 105 , 473–485 (1989).

    Article  CAS  PubMed  Google Scholar 

  13. Jaffredo, T., Gautier, R., Eichmann, A. & Dieterlen-Lievre, F. Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny . Development 125, 4575– 4583 (1998).This paper reported data in favour of the origin of haematopoietic cells from the vasculature. This work supports the concept of ‘haemogenic endothelium’.

    Article  CAS  PubMed  Google Scholar 

  14. Pardanaud, L. & Dieterlen-Lievre, F. Manipulation of the angiopoietic/hemangiopoietic commitment in the avian embryo. Development 126, 617–627 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J. C. & Keller, G. A common precursor for hematopoietic and endothelial cells. Development 125, 725– 732 (1998).Through in vitro differentiation of embryonic stem cells, this paper provides evidence for the existence of the elusive haemangioblast.

    Article  CAS  PubMed  Google Scholar 

  16. Tavian, M. et al. Aorta-associated CD34+ hematopoietic cells in the early human embryo. Blood 87, 67– 72 (1996).

    Article  CAS  PubMed  Google Scholar 

  17. North, T. et al. Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development 126, 2563– 2575 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Wang, Q. et al. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc. Natl Acad. Sci. USA 93, 3444– 3449 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Okuda, T., Deursen, J. v., Hiebert, S. W., Grosveld, G. & Downing, J. R. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84, 321– 330 (1996).

    Article  CAS  PubMed  Google Scholar 

  20. DeBruijn, M. F. T. R., Speck, N. A., Peeters, M. C. E. & Dzierzak, E. Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. EMBO J. 19, 2465–2474 (2000).

    Article  CAS  Google Scholar 

  21. Nishikawa, S.-I. et al. In vitro generation of lymphohematopoietic cells from endothelial cells purified from murine embryos. Immunity 8, 761–769 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Nishikawa, S. I., Nishikawa, S., Hirashima, M., Matsuyoshi, N. & Kodama, H. Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin1 cells at a diverging point of endothelial and hemopoietic lineages. Development 125, 1747–1757 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  24. Phillips, R. L. et al. The genetic program of hematopoietic stem cells. Science 288, 1635–1640 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  25. Socolovsky, M., Lodish, H. F. & Daley, G. Q. Control of hematopoietic differentiation: lack of specificity in signaling by cytokine receptors. Proc. Natl Acad. Sci. USA 95, 6573–6575 ( 1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Stoffel, R. et al. Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo. Proc. Natl Acad. Sci. USA 96, 698– 702 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Orkin, S. H. in Molecular Biology of B-cell and T-cell Development (eds Monroe, J. G. & Rothenberg, E. V.) 41–54 (Humana, Totowa, New Jersery, 1998).

    Book  Google Scholar 

  28. Weintraub, H. et al. The myoD gene family: nodal point during specification of the muscle cell lineage. Science 251, 761 –766 (1991).

    Article  CAS  PubMed  Google Scholar 

  29. Kulessa, H., Frampton, J. & Graf, T. GATA-1 reprograms avian myelomonocytic cells into eosinophils, thromboblasts and erythroblasts. Genes Dev. 9, 1250–1262 (1995). This paper reports the ability of GATA-1 to alter the phenotype of haematopoietic cells. In contrast to the action of myogenic factors in recipient cells, GATA-1 converts progenitors to three different lineages, depending on the concentration at which it is expressed.

    Article  CAS  PubMed  Google Scholar 

  30. Visvader, J. E., Elefanty, A. G., Strasser, A. & Adams, J. M. GATA-1 but not SCL induces megakaryocytic differentiation in an early myeloid line. EMBO J. 11, 4557– 4564 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Visvader, J. E., Crossley, M., Hill, J., Orkin, S. H. & Adams, J. M. The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line. Mol. Cell. Biol. 15, 634– 641 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Visvader, J. & Adams, J. M. Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression. Blood 82, 1493–1501 (1993).

    Article  CAS  PubMed  Google Scholar 

  33. Nerlov, C., McNagny, K. M., Doderlein, G., Kowenz-Leutz, E. & Graf, T. Distinct C/EBP functions are required for eosinophil lineage commitment and maturation. Genes Dev. 12, 2413–2423 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kelly, L. M. et al. MafB is an inducer of monocytic differentiation. EMBO J. 19, 1987–1997 ( 2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. McDevitt, M. A., Shivdasani, R. A., Fujiwara, Y., Yang, H. & Orkin, S. H. A ‘knockdown’ mutation created by cis-element gene targeting reveals the dependence of red blood cell maturation on the level of transcription factor GATA-1. Proc. Natl Acad. Sci. USA 94, 6781–6785 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. DeKoter, R. P. & Singh, H. Graded levels of PU.1 specify B lymphocyte and macrophage cell fates. Science 288, 1439–1441 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. Lebestky, T., Chang, T., Hartenstein, V. & Banerjee, U. Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science 288, 146– 149 (2000).

    Article  CAS  PubMed  Google Scholar 

  39. Adams, B. et al. Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. Genes Dev. 6, 1589–1607 ( 1992).

    Article  CAS  PubMed  Google Scholar 

  40. Urbanek, P., Wang, Z.-Q., Fetka, I., Wagner, E. R. & Busslinger, M. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell 79, 901–912 ( 1994).

    Article  CAS  PubMed  Google Scholar 

  41. Nutt, S. L., Heavey, B., Rolink, A. G. & Busslinger, M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5 . Nature 401, 556–562 (1999).In this paper the phenotype of Pax5−/− haematopoietic cells is examined. Evidence is provided to show that Pax5 is required to suppress other lineages and direct B-lymphoid differentiation.

    Article  CAS  PubMed  Google Scholar 

  42. Rolink, A. G., Nutt, S. L., Melchers, F. & Busslinger, M. Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Nature 401, 603– 606 (1999).

    Article  CAS  PubMed  Google Scholar 

  43. Busslinger, M., Nutt, S. L. & Rolink, A. G. Lineage commitment in lymphopoiesis. Curr. Opin. Immunol. 12, 151–158 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Zheng, W. & Flavell, R. A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells . Cell 89, 587–596 (1997).

    Article  CAS  PubMed  Google Scholar 

  45. Szabo, S. J. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment . Cell 100, 655–669 (2000).

    Article  CAS  PubMed  Google Scholar 

  46. Pevny, L. et al. Erythroid differentiation in chimeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 349, 257–260 (1991). In this ‘classic’ paper, the requirement for a lineage-restricted haematopoietic transcription factor for differentiation is documented through analysis of chimaeras generated with gene-targeted embryonic stem cells.

    Article  CAS  PubMed  Google Scholar 

  47. Shivadasani, R. A., Fujiwara, Y., McDevitt, M. A. & Orkin, S. H. A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. EMBO J. 16, 3965–3973 ( 1997).

    Article  Google Scholar 

  48. Fujiwara, Y., Browne, C. P., Cunniff, K., Goff, S. C. & Orkin, S. H. Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc. Natl Acad. Sci. USA 93, 12355– 12358 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. McKercher, S. R. et al. Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 15, 5647– 5658 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Scott, E. W., Simon, M. C., Anastasi, J. & Singh, H. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 265, 1573– 1577 (1994).

    Article  CAS  PubMed  Google Scholar 

  51. Moreau-Gachelin, F. et al. Spi-1/PU.1 transgenic mice develop multistep erythroleukemias . Mol. Cell. Biol. 16, 2453– 2463 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Moreau-Gachelin, F. et al. The PU.1 transcription factor is the product of the putative oncogene Spi-1. Cell 61, 1166 (1990).

    Article  Google Scholar 

  53. Rekhtman, N., Radparvar, F., Evans, T. & Skoultchi, A. I. Direction interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Genes Dev. 13, 1398–1411 (1999). This paper presents strong evidence to illustrate that direct antagonism between these transcription factors is critical for the development of different lineages. This work is complemented and extended by Refs 54 – 56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang, P. et al. Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc. Natl Acad. Sci. USA 96, 8705–8710 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  56. Zhang, P. et al. PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA-binding. Blood (in the press).

  57. Querfurth, E. et al. Antagonism between C/EBPβ and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors. Genes Dev. (in the press).

  58. Tsang, A. C. et al. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation . Cell 90, 109–119 (1997).This paper was the first to describe a specific cofactor that modulates the function of GATA-1 in transcription.

    Article  CAS  PubMed  Google Scholar 

  59. Tsang, A. P., Fujiwara, Y., Hom, D. B. & Orkin, S. H. Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes Dev. 12, 1176– 1188 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Deconinck, A. E. et al. FOG acts as a repressor of red blood cell development in Xenopus. Development 127, 2031– 2040 (2000).

    Article  CAS  PubMed  Google Scholar 

  61. Fox, A. H. et al. Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers. EMBO J. 18, 2812–2822 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Georgopoulos, K. et al. The Ikaros gene is required for the development of all lymphoid lineages. Cell 79, 143– 156 (1994).

    Article  CAS  PubMed  Google Scholar 

  63. Georgopoulos, K., Moore, D. D. & Defler, B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science 258, 808–812 (1992).

    Article  CAS  PubMed  Google Scholar 

  64. Wang, J. H. et al. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity 5, 537–549 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  65. Koipally, J. & Georgopoulos, K. Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity . J. Biol. Chem. 275, 19594– 19602 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Eberhard, D., Jimenez, G., Heavy, B. & Busslinger, M. Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family. EMBO J. 19, 2292– 2303 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Sieweke, M. H., Tekotte, H., Frampton, J. & Graf, T. MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation . Cell 84, 49–60 (1996).

    Article  Google Scholar 

  68. Maitra, S. & Atchison, M. BSAP can repress enhancer activity by targeting PU.1 function. Mol. Cell. Biol. 20, 1911–1922 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jimenez, G., Griffiths, S. D., Ford, A. M., Greaves, M. F. & Enver, T. Activation of the β-globin locus control region precedes commitment to the erythroid lineage. Proc. Natl Acad. Sci. USA 89, 10618–10622 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hu, M. et al. Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev. 11, 774– 785 (1997).Single-cell RT–PCR was used in this study to show that multipotential progenitor cells contain transcripts usually associated with different lineages.

    Article  CAS  PubMed  Google Scholar 

  71. Tsai, S.-F., Strauss, E. & Orkin, S. H. Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes Dev. 5, 919– 931 (1991).

    Article  CAS  PubMed  Google Scholar 

  72. Chen, H. et al. PU.1 (Spi-1) autoregulates its expression in myeloid cells. Oncogene 19, 1549–1560 ( 1995).

    Google Scholar 

  73. Nutt, S. L. et al. Independent regulation of the two Pax5 alleles during B-cell development. Nature Genet. 21, 390– 395 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Nutt, S. L. & Busslinger, M. Monoallelic expression of Pax5: a paradigm for the haploinsufficiency of mammalian Pax genes? Biol. Chem. 380, 601–611 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Enver, T. & Greaves, M. Loops, lineage, and leukemia. Cell 94, 9–12 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  76. Downing, J. R. The AML1-ETO chimaeric transcription factor in acute myeloid leukaemia: biology and clinical significance. Br. J. Haematol. 106, 296–308 (1999).

    Article  CAS  PubMed  Google Scholar 

  77. Jackson, K. A., Mi, T. & Goodell, M. A. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl Acad. Sci. USA 96, 14482–14486 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gussoni, E. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401, 390– 394 (1999).These two papers show that muscle progenitor cells seem to contribute to haematopoiesis and, conversely, that haematopoietic progenitors give rise to muscle in transplanted mice. In Ref. 77 , it is shown that in vitro culture of muscle progenitors seems to augment haematopoietic reconstitution.

    CAS  PubMed  Google Scholar 

  79. Wood, H. B., May, G., Healy, L., Enver, T. & Morriss-Kay, G. M. CD34 expression patterns during early mouse development are related to modes of blood vessel formation and reveal additional sites of hematopoiesis. Blood 90, 2300– 2311 (1997).

    Article  CAS  PubMed  Google Scholar 

  80. Bjornson, C. R., Rietze, R. L., Reynolds, B. A., Magli, M. C. & Vescovi, A. L. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283, 534–537 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  81. Clarke, D. L. et al. Generalized potential of adult neural stem cells. Science 288, 1660–1663 ( 2000).These two papers indicate that adult neural stem cells have diverse developmental potentials when introduced into mice, chicken embryos, or examined in vitro in embryoid bodies.

    Article  CAS  PubMed  Google Scholar 

  82. Petersen, B. E. et al. Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  83. Theise, N. D. et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 31, 235–240 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Blau, H. M. & Baltimore, D. Differentiation requires continuous regulation. J. Cell Biol. 112, 781– 783 (1991).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Owing to space constraints it has not been possible to cite all relevant publications. I especially thank those investigators who generously communicated findings before publication. S.H.O. is an investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Division of Hematology, Children's Hospital, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Stuart H. Orkin

Authors
  1. Stuart H. Orkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASE LINKS

BMP-4

runx1

myb

ets

GATA-1

GATA-2

GATA-3

MafB

serpent

lozenge

Pax5

T-bet

IL-4

IFNγ

Spi-1

Ikaros

Groucho

myoD

SCL/tal-1

Tel

C/EBP

E2A

FURTHER INFORMATION

Stem cell database

Stuart Orkin's research interests

Encyclopedia of life sciences article entitled Blood cell: lineage restriction

Glossary

HAEMATOPOIETIC STEM CELL

Cell that upon transplantation to an appropriately conditioned recipient reconstitutes the entire haematopoietic system.

MESODERM

Third germ layer in the embryo, formed during the process of gastrulation.

BLOOD ISLANDS

Structures in the extraembryonic yolk sac, composed of endothelial cells, primitive erythrocytes and underlying endoderm.

HAEMANGIOBLAST

Cell which is bipotential for vascular and haematopoietic development.

ENDOTHELIAL CELL

Vascular cell.

ZINC-FINGER

Protein module in which cysteine or cysteine-histidine residues coordinate a zinc ion. Zinc-fingers are often used in DNA recognition and also in protein–protein interactions.

B-ZIPPER

Class of transcription factors in which a basic domain involved in DNA recognition neighbours a region of repeating hydrophobic amino acids that mediate protein dimerization. Members include c-Jun, C/EBP and myogenic factors.

CYTOKINES

Polypeptide haematopoietic regulatory factors, such as erythropoietin and colony-stimulating factors.

AUTOREGULATION

Positive feedback regulation by a transcription factor on expression from its own gene.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orkin, S. Diversification of haematopoietic stem cells to specific lineages. Nat Rev Genet 1, 57–64 (2000). https://doi.org/10.1038/35049577

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35049577

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing