Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cb9f654ff-nr592 Total loading time: 0 Render date: 2025-08-08T11:22:50.255Z Has data issue: false hasContentIssue false

1 - A Developmental Approach to Hematopoiesis

from SECTION ONE - THE MOLECULAR, CELLULAR, AND GENETIC BASIS OF HEMOGLOBIN DISORDERS

Published online by Cambridge University Press:  03 May 2010

Martin H. Steinberg ,
Bernard G. Forget ,
Douglas R. Higgs  and
David J. Weatherall
By
Elaine Dzierzak
Martin H. Steinberg
Affiliation:
Boston University
Bernard G. Forget
Affiliation:
Yale University, Connecticut
Douglas R. Higgs
Affiliation:
MRC Institute of Molecular Medicine, University of Oxford
David J. Weatherall
Affiliation:
Albert Einstein College of Medicine, New York
Get access

Summary

INTRODUCTION AND GENERAL CONSIDERATIONS

During mammalian development, the first morphologically recognizable blood cells in the conceptus are those of the erythroid lineage. The early production of erythroid lineage cells in the yolk sac is required for the development of the vertebrate embryo. These blood cells are short-lived, however. In contrast, long-term adult hematopoiesis results from a complex cell lineage differentiation hierarchy that produces at least eight functionally distinct lineages of differentiated blood cells. The founder cells for this hierarchy are the hematopoietic stem cells (HSCs), which undergo progressive differentiation, proliferation, and restriction in lineage potential. The adult blood system is constantly replenished throughout adult life from rare HSCs harbored in the bone marrow. The field of “developmental hematopoiesis” investigates how this complex adult system is generated in the conceptus. Current research interests in this field include 1) the embryonic origins, cell lineage relationships, and functions of the cells within the multiple embryonic hematopoietic compartments; 2) the changing developmental microenvironments that support hematopoietic (stem) cell growth; and 3) the molecular programming of the hematopoietic system during ontogeny. This chapter will focus on our current knowledge concerning the embryonic beginnings of the adult hematopoietic system. Insights emerging from such a developmental approach should lead to novel molecular and cellular manipulations that could aid in the ex vivo generation and/or expansion of HSCs and progenitors for clinical use in transplantations for leukemias or blood-related genetic disease.

Information

Type
Chapter
Information
Disorders of Hemoglobin
Genetics, Pathophysiology, and Clinical Management
 , pp. 3 - 23
Publisher: Cambridge University Press
Print publication year: 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Dieterlen-Lievre, F, Le, Douarin NM. Developmental rules in the hematopoietic and immune systems of birds: how general are they?Seminars in Developmental Biology 1993;4(6):325–32.CrossRefGoogle Scholar
Jaffredo, T, Nottingham, W, Liddiard, K, Bollerot, K, Pouget, C, Bruijn, M. From hemangioblast to hematopoietic stem cell: an endothelial connection?Exp Hematol 2005;33(9):1029–40.CrossRefGoogle Scholar
Dzierzak, E, Speck, NA. Of lineage and legacy: the development of mammalian hematopoietic stem cells. Nat Immunol 2008;9(2):129–36.CrossRefGoogle ScholarPubMed
McKenzie, JL, Gan, OI, Doedens, M, Wang, JC, Dick, JE. Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment. Nat Immunol 2006;7(11):1225–33.CrossRefGoogle ScholarPubMed
Park, C, Lugus, JJ, Choi, K. Stepwise commitment from embryonic stem to hematopoietic and endothelial cells. Curr Top Dev Biol 2005;66:1–36.CrossRefGoogle ScholarPubMed
Zambidis, ET, Peault, B, Park, TS, Bunz, F, Civin, CI. Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development. Blood 2005;106(3):860–70.CrossRefGoogle ScholarPubMed
Miale, J. Laboratory medicine Hematology. Sixth edition ed. St. Louis: The C. V. Mosby Company; 1982.Google Scholar
Nieuwkoop, P. The formation of mesoderm in Urodelean amphibians. I. Induction by the endoderm. Roux Arch Entw Mech Org 1969;162:341–73.CrossRefGoogle ScholarPubMed
Dale, L, Smith, JC, Slack, JM. Mesoderm induction in Xenopus laevis: a quantitative study using a cell lineage label and tissue-specific antibodies. J Embryol Exp Morphol 1985;89:289–312.Google ScholarPubMed
Nieuwkoop, P, Ubbels, G. The formation of mesoderm in Urodelean amphibians. IV. Quantitative evidence for the purely ‘ectodermal’ origin of the entire mesoderm and of the pharyngeal endoderm. Roux Arch Entw Mech Org 1972;169:185–99.Google ScholarPubMed
Rodaway, A, Patient, R. Mesendoderm. an ancient germ layer?Cell 2001;105(2):169–72.CrossRefGoogle ScholarPubMed
Wardle, FC, Smith, JC. Transcriptional regulation of mesendoderm formation in Xenopus. Semin Cell Dev Biol 2006;17(1):99–109.CrossRefGoogle ScholarPubMed
Smith, JC. Mesoderm-inducing factors in early vertebrate development. Embo J 1993;12(12):4463–70.Google ScholarPubMed
Stennard, F, Ryan, K, Gurdon, JB. Markers of vertebrate mesoderm induction. Curr Opin Genet Dev 1997;7(5):620–7.CrossRefGoogle ScholarPubMed
Lawson, KA, Meneses, JJ, Pedersen, RA. Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development 1991;113(3):891–911.Google ScholarPubMed
Kinder, SJ, Tsang, TE, Quinlan, GA, Hadjantonakis, AK, Nagy, A, Tam, PP. The orderly allocation of mesodermal cells to the extraembryonic structures and the anteroposterior axis during gastrulation of the mouse embryo. Development 1999;126(21):4691–701.Google ScholarPubMed
Kanatsu, M, Nishikawa, SI. In vitro analysis of epiblast tissue potency for hematopoietic cell differentiation. Development 1996;122(3):823–30.Google ScholarPubMed
Russell, ES, Bernstein, SE. Blood and blood formation. In: Green, EL, ed. Biology of the laboratory mouse. 2nd ed. New York: McGraw-Hill; 1966:351–72.Google Scholar
Tavian, M, Peault, B. Embryonic development of the human hematopoietic system. Int J Dev Biol 2005;49(2–3):243–50.CrossRefGoogle ScholarPubMed
Miura, Y, Wilt, FH. Tissue interaction and the formation of the first erythroblasts of the chick embryo. Dev Biol 1969; 19(2):201–11.CrossRefGoogle ScholarPubMed
Pardanaud, L, Dieterlen-Lievre, F. Manipulation of the angiopoietic/hemangiopoietic commitment in the avian embryo. Development 1999;126(4):617–27.Google ScholarPubMed
Belaoussoff, M, Farrington, SM, Baron, MH. Hematopoietic induction and respecification of A-P identity by visceral endoderm signaling in the mouse embryo. Development 1998;125(24):5009–18.Google ScholarPubMed
Dyer, MA, Farrington, SM, Mohn, D, Munday, , Baron, MH. Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo. Development 2001;128(10):1717–30.Google ScholarPubMed
Murray, P. The development in vitro of the blood of the early chick embryo. Proc Roy Soc London 1932;11:497–521.CrossRefGoogle Scholar
Sabin, F. Studies on the origin of blood vessels and of red blood corpuscles as seen in the living blastoderm of chicks during the second day of incubation. Carnegie Inst Wash Pub # 272, Contrib Embryol 1920;9:214.Google Scholar
Park, C, Ma, YD, Choi, K. Evidence for the hemangioblast. Exp Hematol 2005;33(9):965–70.CrossRefGoogle ScholarPubMed
Shalaby, F, Rossant, J, Yamaguchi, TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995;376(6535):62–6.CrossRefGoogle ScholarPubMed
Tavian, M, Hallais, MF, Peault, B. Emergence of intraembryonic hematopoietic precursors in the pre-liver human embryo. Development 1999;126(4):793–803.Google ScholarPubMed
Palis, J, Robertson, S, Kennedy, M, Wall, C, Keller, G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 1999; 126(22):5073–84.Google ScholarPubMed
Fehling, HJ, Lacaud, G, Kubo, A, et al. Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation. Development 2003; 130(17):4217–27.CrossRefGoogle ScholarPubMed
Huber, TL, Kouskoff, V, Fehling, HJ, Palis, J, Keller, G. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 2004;432(7017):625–30.CrossRefGoogle ScholarPubMed
Ueno, H, Weissman, IL. Clonal analysis of mouse development reveals a polyclonal origin for yolk sac blood islands. Dev Cell 2006;11(4):519–33.CrossRefGoogle ScholarPubMed
Corbel, C, Salaun, J, Belo-Diabangouaya, P, Dieterlen-Lievre, F. Hematopoietic potential of the pre-fusion allantois. Dev Biol 2007;301(2):478–88.CrossRefGoogle ScholarPubMed
Zeigler, BM, Sugiyama, D, Chen, M, Guo, Y, Downs, KM, Speck, NA. The allantois and chorion, when isolated before circulation or chorio-allantoic fusion, have hematopoietic potential. Development 2006;133(21):4183–92.CrossRefGoogle ScholarPubMed
Caprioli, A, Minko, K, Drevon, C, Eichmann, A, Dieterlen-Lievre, F, Jaffredo, T. Hemangioblast commitment in the avian allantois: cellular and molecular aspects. Dev Biol 2001;238(1):64–78.CrossRefGoogle ScholarPubMed
Caprioli, A, Jaffredo, T, Gautier, R, Dubourg, C, Dieterlen-Lievre, F. Blood-borne seeding by hematopoietic and endothelial precursors from the allantois. Proc Natl Acad Sci U S A 1998;95(4):1641–6.CrossRefGoogle ScholarPubMed
Downs, KM. The murine allantois. Curr Top Dev Biol 1998;39:1–33.CrossRefGoogle ScholarPubMed
Alvarez-Silva, M, Belo-Diabangouaya, P, Salaun, J, Dieterlen-Lievre F. Mouse placenta is a major hematopoietic organ. Development 2003;130(22):5437–44.CrossRefGoogle ScholarPubMed
Gekas, C, Dieterlen-Lievre, F, Orkin, SH, Mikkola, HK. The placenta is a niche for hematopoietic stem cells. Dev Cell 2005;8(3):365–75.CrossRefGoogle ScholarPubMed
Ottersbach, K, Dzierzak, E. The murine placenta contains hematopoietic stem cells within the vascular labyrinth region. Dev Cell 2005;8(3):377–87.CrossRefGoogle ScholarPubMed
Dieterlen-Lievre, F. On the origin of haemopoietic stem cells in the avian embryo: an experimental approach. J Embryol Exp Morphol 1975;33(3):607–19.Google Scholar
Beaupain, D, Martin, C, Dieterlen-Lievre, F. Are developmental hemoglobin changes related to the origin of stem cells and site of erythropoiesis?Blood 1979;53(2):212–25.Google ScholarPubMed
Dieterlen-Lievre, F, Martin, C. Diffuse intraembryonic hemopoiesis in normal and chimeric avian development. Dev Biol 1981;88(1):180–91.CrossRefGoogle ScholarPubMed
Martin, C, Beaupain, D, Dieterlen-Lievre, F. Developmental relationships between vitelline and intra-embryonic haemopoiesis studied in avian ‘yolk sac chimaeras’. Cell Differ 1978;7(3):115–30.CrossRefGoogle ScholarPubMed
Cormier, F, Dieterlen-Lievre, F. The wall of the chick embryo aorta harbours M-CFC, G-CFC, GM-CFC and BFU-E. Development 1988;102(2):279–85.Google ScholarPubMed
Jaffredo, T, Gautier, R, Brajeul, V, Dieterlen-Lievre, F. Tracing the progeny of the aortic hemangioblast in the avian embryo. Dev Biol 2000;224(2):204–14.CrossRefGoogle ScholarPubMed
Jaffredo, T, Gautier, R, Eichmann, A, Dieterlen-Lievre, F. Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny. Development 1998;125(22):4575–83.Google ScholarPubMed
Kau, CL, Turpen, JB. Dual contribution of embryonic ventral blood island and dorsal lateral plate mesoderm during ontogeny of hemopoietic cells in Xenopus laevis. J Immunol 1983;131(5):2262–6.Google ScholarPubMed
Maeno, M, Tochinai, S, Katagiri, C. Differential participation of ventral and dorsolateral mesoderms in the hemopoiesis of Xenopus, as revealed in diploid-triploid or interspecific chimeras. Dev Biol 1985;110(2):503–8.CrossRefGoogle ScholarPubMed
Turpen, JB, Knudson, CM, Hoefen, PS. The early ontogeny of hematopoietic cells studied by grafting cytogenetically labeled tissue anlagen: localization of a prospective stem cell compartment. Dev Biol 1981;85(1):99–112.CrossRefGoogle ScholarPubMed
Turpen, JB, Knudson, CM. Ontogeny of hematopoietic cells in Rana pipiens: precursor cell migration during embryogenesis. Dev Biol 1982;89(1):138–51.CrossRefGoogle ScholarPubMed
Ciau-Uitz, A, Walmsley, M, Patient, R. Distinct origins of adult and embryonic blood in Xenopus. Cell 2000;102(6):787–96.CrossRefGoogle ScholarPubMed
Turpen, JB, Kelley, CM, Mead, PE, Zon, LI. Bipotential primitive-definitive hematopoietic progenitors in the vertebrate embryo. Immunity 1997;7(3):325–34.CrossRefGoogle ScholarPubMed
Medvinsky, A, Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 1996;86(6): 897–906.CrossRefGoogle ScholarPubMed
Muller, AM, Medvinsky, A, Strouboulis, J, Grosveld, F, Dzierzak, E. Development of hematopoietic stem cell activity in the mouse embryo. Immunity 1994;1(4):291–301.CrossRefGoogle ScholarPubMed
Dzierzak, E. The emergence of definitive hematopoietic stem cells in the mammal. Curr Opin Hematol 2005;12(3):197–202.CrossRefGoogle ScholarPubMed
Cumano, A, Dieterlen-Lievre, F, Godin, I. Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 1996;86(6):907–16.CrossRefGoogle ScholarPubMed
Medvinsky, AL, Samoylina, NL, Müller, AM, Dzierzak, E. An early pre-liver intraembryonic source of CFU-S in the developing mouse. Nature 364; 64–67.
Godin, IE, Garcia-Porrero, JA, Coutinho, A, Dieterlen-Lievre, F, Marcos, MA. Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors. Nature 1993;364(6432):67–70.CrossRefGoogle ScholarPubMed
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 U S A 1995;92(3):773–7.CrossRefGoogle ScholarPubMed
Bruijn, MF, Speck, NA, Peeters, MC, Dzierzak, E. Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. Embo J 2000;19(11):2465–74.CrossRefGoogle ScholarPubMed
Garcia-Porrero, JA, Godin, IE, Dieterlen-Lievre, F. Potential intraembryonic hemogenic sites at pre-liver stages in the mouse. Anat Embryol (Berl) 1995;192(5):425–35.CrossRefGoogle ScholarPubMed
Tavian, M, Coulombel, L, Luton, D, Clemente, HS, Dieterlen-Lievre, F, Peault, B. Aorta-associated CD34+ hematopoietic cells in the early human embryo. Blood 1996;87(1):67–72.Google ScholarPubMed
Wood, HB, May, G, Healy, L, Enver, T, Morriss-Kay, GM. CD34 expression patterns during early mouse development are related to modes of blood vessel formation and reveal additional sites of hematopoiesis. Blood 1997;90(6):2300–11.Google ScholarPubMed
North, T, Gu, TL, Stacy, T, et al. Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development 1999;126(11):2563–75.Google ScholarPubMed
Okuda, T, Deursen, J, Hiebert, SW, Grosveld, G, Downing, JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 1996;84(2):321–30.CrossRefGoogle ScholarPubMed
Wang, Q, Stacy, T, Binder, M, Marin-Padilla, M, Sharpe, AH, Speck, NA. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci U S A 1996;93(8):3444–9.CrossRefGoogle ScholarPubMed
Bruijn, MF, Ma, X, Robin, C, Ottersbach, K, Sanchez, MJ, Dzierzak, E. Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta. Immunity 2002;16(5):673–83.CrossRefGoogle ScholarPubMed
Moore, MA, 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 1970;18(3):279–96.CrossRefGoogle ScholarPubMed
Fassler, R, Meyer, M. Consequences of lack of beta 1 integrin gene expression in mice. Genes Dev 1995;9(15):1896–908.CrossRefGoogle Scholar
Hirsch, E, Iglesias, A, Potocnik, AJ, Hartmann, U, Fassler, R. Impaired migration but not differentiation of haematopoietic stem cells in the absence of beta1 integrins. Nature 1996;380(6570):171–5.CrossRefGoogle Scholar
Ema, H, Nakauchi, H. Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 2000;95(7):2284–8.Google ScholarPubMed
Houssaint, E. Differentiation of the mouse hepatic primordium. II. Extrinsic origin of the haemopoietic cell line. Cell Differ 1981;10(5):243–52.CrossRefGoogle ScholarPubMed
Johnson, GR, Moore, MA. Role of stem cell migration in initiation of mouse foetal liver haemopoiesis. Nature 1975;258(5537):726–8.CrossRefGoogle ScholarPubMed
Kumaravelu, P, Hook, L, Morrison, AM, et al. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad- mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. Development 2002;129(21):4891–9.Google ScholarPubMed
Metcalf, D. The hemopoietic colony stimulating factors. Amsterdam: Elsevier Science Publishers B. V.; 1984.Google Scholar
Adolfsson, J, Borge, OJ, Bryder, D, et al. Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 2001;15(4):659–69.CrossRefGoogle ScholarPubMed
Kelemen, E, Calvo, W, Fliedner, T. Atlas of Human Hemopoietic Development. Berlin: Springer-Verlag; 1979.CrossRefGoogle Scholar
Ferkowicz, MJ, Yoder, MC. Blood island formation: longstanding observations and modern interpretations. Exp Hematol 2005;33(9):1041–7.CrossRefGoogle ScholarPubMed
Wong, PM, Chung, SW, Reicheld, SM, Chui, DH. Hemoglobin switching during murine embryonic development: evidence for two populations of embryonic erythropoietic progenitor cells. Blood 1986;67(3):716–21.Google ScholarPubMed
Kovach, JS, Marks, PA, Russell, ES, Epler, H. Erythroid cell development in fetal mice: ultrastructural characteristics and hemoglobin synthesis. J Mol Biol 1967;25(1):131–42.CrossRefGoogle ScholarPubMed
Rifkind, RA, Chui, D, Epler, H. An ultrastructural study of early morphogenetic events during the establishment of fetal hepatic erythropoiesis. J Cell Biol 1969;40(2):343–65.CrossRefGoogle ScholarPubMed
Grosveld, F, Dillon, N, Higgs, D. The regulation of human globin gene expression. Baillieres Clin Haematol 1993;6(1): 31–55.CrossRefGoogle ScholarPubMed
Russell, ES. Hereditary anemias of the mouse: a review for geneticists. Adv Genet 1979;20:357–459.Google ScholarPubMed
Kennedy, M, Firpo, M, Choi, K, et al. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 1997;386(6624):488–93.CrossRefGoogle ScholarPubMed
Wijgerde, M, Grosveld, F, Fraser, P. Transcription complex stability and chromatin dynamics in vivo. Nature 1995; 377(6546):209–13.CrossRefGoogle ScholarPubMed
Nakano, T, Kodama, H, Honjo, T. In vitro development of primitive and definitive erythrocytes from different precursors. Science 1996;272(5262):722–4.CrossRefGoogle ScholarPubMed
Ogawa, M, Matsuzaki, Y, Nishikawa, S, et al. Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med 1991;174(1):63–71.CrossRefGoogle ScholarPubMed
McGrath, KE, Palis, J. Hematopoiesis in the yolk sac: more than meets the eye. Exp Hematol 2005;33(9):1021–8.CrossRefGoogle ScholarPubMed
Naito, M, Umeda, S, Yamamoto, T, et al. Development, differentiation, and phenotypic heterogeneity of murine tissue macrophages. J Leukoc Biol 1996;59(2):133–8.CrossRefGoogle ScholarPubMed
Bonifer, C, Faust, N, Geiger, H, Muller, AM. Developmental changes in the differentiation capacity of haematopoietic stem cells. Immunol Today 1998;19(5):236–41.CrossRefGoogle ScholarPubMed
Eren, R, Zharhary, D, Abel, L, Globerson, A. Ontogeny of T cells: development of pre-T cells from fetal liver and yolk sac in the thymus microenvironment. Cell Immunol 1987;108(1):76–84.CrossRefGoogle ScholarPubMed
Liu, CP, Auerbach, R. In vitro development of murine T cells from prethymic and preliver embryonic yolk sac hematopoietic stem cells. Development 1991;113(4):1315–23.Google ScholarPubMed
Ogawa, M, Nishikawa, S, Ikuta, K, et al. B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stromal cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac. Embo J 1988;7(5):1337–43.Google ScholarPubMed
Delassus, S, Cumano, A. Circulation of hematopoietic progenitors in the mouse embryo. Immunity 1996;4(1):97–106.CrossRefGoogle ScholarPubMed
Ikuta, K, Kina, T, MacNeil, I, et al. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell 1990;62(5):863–74.CrossRefGoogle ScholarPubMed
Herzenberg, , Stall, AM, Lalor, PA, et al. The Ly-1 B cell lineage. Immunol Rev 1986;93:81–102.CrossRefGoogle ScholarPubMed
Cumano, A, Furlonger, C, Paige, CJ. Differentiation and characterization of B-cell precursors detected in the yolk sac and embryo body of embryos beginning at the 10- to 12-somite stage. Proc Natl Acad Sci U S A 1993;90(14):6429–33.CrossRefGoogle ScholarPubMed
Johnson, GR, Barker, DC. Erythroid progenitor cells and stimulating factors during murine embryonic and fetal development. Exp Hematol 1985;13(3):200–8.Google ScholarPubMed
Sonoda, T, Hayashi, C, Kitamura, Y. Presence of mast cell precursors in the yolk sac of mice. Dev Biol 1983;97(1):89–94.CrossRefGoogle Scholar
Ferkowicz, MJ, Starr, M, Xie, X, et al. CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo. Development 2003;130(18):4393–403.CrossRefGoogle ScholarPubMed
Rampon, C, Huber, P. Multilineage hematopoietic progenitor activity generated autonomously in the mouse yolk sac: analysis using angiogenesis-defective embryos. Int J Dev Biol 2003;47(4):273–80.Google ScholarPubMed
Lux, CT, Yoshimoto, M, McGrath, K, Conway, SJ, Palis, J, Yoder, MC. All primitive and definitive hematopoietic progenitor cells emerging prior to E10 in the mouse embryo are products of the yolk sac. Blood 2007.Google Scholar
Yashiro, K, Shiratori, H, Hamada, H. Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch. Nature 2007;450(7167):285–8.CrossRefGoogle ScholarPubMed
Migliaccio, G, Migliaccio, AR, Petti, S, et al. Human embryonic hemopoiesis. Kinetics of progenitors and precursors underlying the yolk sac–liver transition. J Clin Invest 1986;78(1):51–60.CrossRefGoogle ScholarPubMed
Huyhn, A, Dommergues, M, Izac, B, et al. Characterization of hematopoietic progenitors from human yolk sacs and embryos. Blood 1995;86(12):4474–85.Google ScholarPubMed
Peault, B. Hematopoietic stem cell emergence in embryonic life: developmental hematology revisited. J Hematother 1996;5(4):369–78.CrossRefGoogle ScholarPubMed
Till, JE, Mc, CE. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 1961;14:213–22.CrossRefGoogle ScholarPubMed
Bruijn, MF, Peeters, MC, Luteijn, T, Visser, P, Speck, NA, Dzierzak, E. CFU-S(11) activity does not localize solely with the aorta in the aorta-gonad-mesonephros region. Blood 2000;96(8):2902–4.Google Scholar
Tavian, M, Robin, C, Coulombel, L, Peault, B. The human embryo, but not its yolk sac, generates lympho-myeloid stem cells: mapping multipotent hematopoietic cell fate in intraembryonic mesoderm. Immunity 2001;15(3):487–95.CrossRefGoogle Scholar
Yoder, MC, Hiatt, K, Dutt, P, Mukherjee, P, Bodine, DM, Orlic, D. Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac. Immunity 1997;7(3):335–44.CrossRefGoogle ScholarPubMed
Toles, JF, Chui, DH, Belbeck, LW, Starr, E, Barker, JE. Hemopoietic stem cells in murine embryonic yolk sac and peripheral blood. Proc Natl Acad Sci U S A 1989;86(19):7456–9.CrossRefGoogle ScholarPubMed
Weissman, I VP, Gardner, R. Fetal hematopoietic origins of the adult hematolymphoid system. Cold Spring Harbor: Cold Spring Harbor Laboratory; 1978.Google Scholar
Sugiyama, D, Ogawa, M, Hirose, I, Jaffredo, T, Arai, K, Tsuji, K. Erythropoiesis from acetyl LDL incorporating endothelial cells at the preliver stage. Blood 2003;101(12):4733–8.CrossRefGoogle ScholarPubMed
Ling, KW, Ottersbach, K, Hamburg, JP, et al. GATA-2 plays two functionally distinct roles during the ontogeny of hematopoietic stem cells. J Exp Med 2004;200(7):871–82.CrossRefGoogle ScholarPubMed
Minegishi, N, Ohta, J, Yamagiwa, H, et al. The mouse GATA-2 gene is expressed in the para-aortic splanchnopleura and aorta-gonads and mesonephros region. Blood 1999;93(12): 4196–207.Google ScholarPubMed
North, TE, Bruijn, MF, Stacy, T, et al. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 2002;16(5):661–72.CrossRefGoogle ScholarPubMed
Sanchez, MJ, Bockamp, EO, Miller, J, Gambardella, L, Green, AR. Selective rescue of early haematopoietic progenitors in Scl(−/−) mice by expressing Scl under the control of a stem cell enhancer. Development 2001;128(23):4815–27.Google ScholarPubMed
Sanchez, MJ, Holmes, A, Miles, C, Dzierzak, E. Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo. Immunity 1996;5(6):513–25.CrossRefGoogle ScholarPubMed
Taoudi, S, Morrison, AM, Inoue, H, Gribi, R, Ure, J, Medvinsky, A. Progressive divergence of definitive haematopoietic stem cells from the endothelial compartment does not depend on contact with the foetal liver. Development 2005;132(18):4179–91.CrossRefGoogle Scholar
Ody, C, Vaigot, P, Quere, P, Imhof, BA, Corbel, C. Glycoprotein IIb-IIIa is expressed on avian multilineage hematopoietic progenitor cells. Blood 1999;93(9):2898–906.Google ScholarPubMed
Durand, C, Robin, C, Bollerot, K, Baron, MH, Ottersbach, K, Dzierzak, E. Embryonic stromal clones reveal developmental regulators of definitive hematopoietic stem cells. Proc Natl Acad Sci U S A 2007;104(52):20838–43.CrossRefGoogle ScholarPubMed
Taoudi, S, Medvinsky, A. Functional identification of the hematopoietic stem cell niche in the ventral domain of the embryonic dorsal aorta. Proc Natl Acad Sci U S A 2007; 104(22):9399–403.CrossRefGoogle ScholarPubMed
Bertrand, JY, Giroux, S, Golub, R, et al. Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin. Proc Natl Acad Sci U S A 2005; 102(1):134–9.CrossRefGoogle ScholarPubMed
Oberlin, E, Tavian, M, Blazsek, I, Peault, B. Blood-forming potential of vascular endothelium in the human embryo. Development 2002;129(17):4147–57.Google ScholarPubMed
Moore, MA, Owen, JJ. Experimental studies on the development of the thymus. J Exp Med 1967;126(4):715–26.CrossRefGoogle ScholarPubMed
Douarin, NM, Dieterlen-Lievre, F, Oliver, PD. Ontogeny of primary lymphoid organs and lymphoid stem cells. Am J Anat 1984;170(3):261–99.CrossRefGoogle ScholarPubMed
Chen, XD, Turpen, JB. Intraembryonic origin of hepatic hematopoiesis in Xenopus laevis. J Immunol 1995;154(6): 2557–67.Google ScholarPubMed
Kissa, K, Murayama, E, Zapata, A, et al. Live imaging of emerging hematopoietic stem cells and early thymus colonization. Blood 2008;111(3):1147–56.CrossRefGoogle ScholarPubMed
Bechtold, TE, Smith, PB, Turpen, JB. Differential stem cell contributions to thymocyte succession during development of Xenopus laevis. J Immunol 1992;148(10):2975–82.Google ScholarPubMed
Cudennec, CA, Thiery, JP, Douarin, NM. In vitro induction of adult erythropoiesis in early mouse yolk sac. Proc Natl Acad Sci U S A 1981;78(4):2412–6.CrossRefGoogle ScholarPubMed
Bertrand, JY, Desanti, GE, Lo-Man, R, Leclerc, C, Cumano, A, Golub, R. Fetal spleen stroma drives macrophage commitment. Development 2006;133(18):3619–28.CrossRefGoogle ScholarPubMed
Yokota, T, Huang, J, Tavian, M, et al. Tracing the first waves of lymphopoiesis in mice. Development 2006;133(10):2041–51.CrossRefGoogle ScholarPubMed
Jotereau, FV, Douarin, NM. Demonstration of a cyclic renewal of the lymphocyte precursor cells in the quail thymus during embryonic and perinatal life. J Immunol 1982;129(5):1869–77.Google ScholarPubMed
Ewijk, W, Hollander, G, Terhorst, C, Wang, B. Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets. Development 2000;127(8):1583–91.Google ScholarPubMed
Xie, H, Ye, M, Feng, R, Graf, T. Stepwise reprogramming of B cells into macrophages. Cell 2004;117(5):663–76.CrossRefGoogle ScholarPubMed
Gothert, JR, Gustin, SE, Hall, MA, et al. In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis. Blood 2005;105(7):2724–32.CrossRefGoogle ScholarPubMed
Samokhvalov, IM, Samokhvalova, NI, Nishikawa, S. Cell tracing shows the contribution of the yolk sac to adult haematopoiesis. Nature 2007;446(7139):1056–61.CrossRefGoogle ScholarPubMed
Abbott, A. Biologists claim Nobel prize with a knock-out. Nature 2007;449(7163):642.CrossRefGoogle ScholarPubMed
Dale, L, Howes, G, Price, BM, Smith, JC. Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. Development 1992;115(2):573–85.Google ScholarPubMed
Mead, PE, Brivanlou, IH, Kelley, CM, Zon, LI. BMP-4-responsive regulation of dorsal-ventral patterning by the homeobox protein Mix.1. Nature 1996;382(6589):357–60.CrossRefGoogle ScholarPubMed
Walmsley, M, Ciau-Uitz, A, Patient, R. Adult and embryonic blood and endothelium derive from distinct precursor populations which are differentially programmed by BMP in Xenopus. Development 2002;129(24):5683–95.CrossRefGoogle ScholarPubMed
Walmsley, M, Cleaver, D, Patient, R. Fibroblast growth factor controls the timing of Scl, Lmo2, and Runx1 expression during embryonic blood development. Blood 2008;111(3):1157–66.CrossRefGoogle ScholarPubMed
Wilt, FH. Erythropoiesis in the Chick Embryo: The Role of Endoderm. Science 1965;147:1588–90.CrossRefGoogle ScholarPubMed
Tonegawa, A, Funayama, N, Ueno, N, Takahashi, Y. Mesodermal subdivision along the mediolateral axis in chicken controlled by different concentrations of BMP-4. Development 1997;124(10):1975–84.Google ScholarPubMed
Gering, M, Patient, R. Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell 2005;8(3):389–400.CrossRefGoogle ScholarPubMed
Byrd, N, Becker, S, Maye, P, et al. Hedgehog is required for murine yolk sac angiogenesis. Development 2002;129(2): 361–72.Google ScholarPubMed
Winnier, G, Blessing, M, Labosky, PA, Hogan, BL. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 1995;9(17):2105–16.CrossRefGoogle ScholarPubMed
Dickson, MC, Martin, JS, Cousins, FM, Kulkarni, AB, Karlsson, S, Akhurst, RJ. Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 1995;121(6):1845–54.Google ScholarPubMed
Karlsson, G, Blank, U, Moody, JL, et al. Smad4 is critical for self-renewal of hematopoietic stem cells. J Exp Med 2007;204(3):467–74.CrossRefGoogle ScholarPubMed
Johansson, BM, Wiles, MV. Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. Mol Cell Biol 1995;15(1):141–51.CrossRefGoogle ScholarPubMed
Marshall, CJ, Kinnon, C, Thrasher, AJ. Polarized expression of bone morphogenetic protein-4 in the human aorta-gonad-mesonephros region. Blood 2000;96(4):1591–3.Google ScholarPubMed
Sadlon, TJ, Lewis, ID, D'Andrea, RJ. BMP4: its role in development of the hematopoietic system and potential as a hematopoietic growth factor. Stem Cells 2004;22(4):457–74.CrossRefGoogle ScholarPubMed
Carmeliet, P, Ferreira, V, Breier, G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996;380(6573):435–9.CrossRefGoogle ScholarPubMed
Ferrara, N, Carver-Moore, K, Chen, H, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996;380(6573):439–42.CrossRefGoogle ScholarPubMed
Choi, K, Kennedy, M, Kazarov, A, Papadimitriou, JC, Keller, G. A common precursor for hematopoietic and endothelial cells. Development 1998;125(4):725–32.Google ScholarPubMed
Kumano, K, Chiba, S, Kunisato, A, et al. Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells. Immunity 2003;18(5):699–711.CrossRefGoogle Scholar
Robert-Moreno, A, Espinosa, L, Pompa, JL, Bigas, A. RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells. Development 2005;132(5):1117–26.CrossRefGoogle ScholarPubMed
Burns, CE, Traver, D, Mayhall, E, Shepard, JL, Zon, LI. Hematopoietic stem cell fate is established by the Notch-Runx pathway. Genes Dev 2005;19(19):2331–42.CrossRefGoogle ScholarPubMed
Nakagawa, M, Ichikawa, M, Kumano, K, et al. AML1/Runx1 rescues Notch1-null mutation-induced deficiency of paraaortic splanchnopleural hematopoiesis. Blood 2006;108(10): 3329–34.CrossRefGoogle Scholar
Bernstein, A. Molecular genetic approaches to the elucidation of hematopoietic stem cell function. Stem Cells 1993;11 Suppl 2:31–5.CrossRefGoogle ScholarPubMed
Witte, ON. Steel locus defines new multipotent growth factor. Cell 1990;63(1):5–6.CrossRefGoogle ScholarPubMed
Okada, S, Nakauchi, H, Nagayoshi, K, et al. Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule. Blood 1991;78(7):1706–12.Google ScholarPubMed
Hassan, HT, Zander, A. Stem cell factor as a survival and growth factor in human normal and malignant hematopoiesis. Acta Haematol 1996;95(3–4):257–62.CrossRefGoogle ScholarPubMed
Porcher, C, Swat, W, Rockwell, K, Fujiwara, Y, Alt, FW, Orkin, SH. The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 1996;86(1):47–57.CrossRefGoogle Scholar
Robb, L, Elwood, NJ, Elefanty, AG, et al. The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse. Embo J 1996;15(16):4123–9.Google ScholarPubMed
Robb, L, Lyons, I, Li, R, et al. Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. Proc Natl Acad Sci U S A 1995;92(15):7075–9.CrossRefGoogle ScholarPubMed
Shivdasani, RA, Mayer, EL, Orkin, SH. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature 1995;373(6513):432–4.CrossRefGoogle ScholarPubMed
Visvader, JE, Fujiwara, Y, Orkin, SH. Unsuspected role for the T-cell leukemia protein SCL/tal-1 in vascular development. Genes Dev 1998;12(4):473–9.CrossRefGoogle ScholarPubMed
Gering, M, Rodaway, AR, Gottgens, B, Patient, RK, Green, AR. The SCL gene specifies haemangioblast development from early mesoderm. Embo J 1998;17(14):4029–45.CrossRefGoogle ScholarPubMed
D'Souza, SL, Elefanty, AG, Keller, G. SCL/Tal-1 is essential for hematopoietic commitment of the hemangioblast but not for its development. Blood 2005;105(10):3862–70.CrossRefGoogle Scholar
Warren, AJ, Colledge, WH, Carlton, MB, Evans, MJ, Smith, AJ, Rabbitts, TH. The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development. Cell 1994;78(1):45–57.CrossRefGoogle ScholarPubMed
Yamada, Y, Warren, AJ, Dobson, C, Forster, A, Pannell, R, Rabbitts, TH. The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis. Proc Natl Acad Sci U S A 1998;95(7):3890–5.CrossRefGoogle Scholar
Landry, JR, Kinston, S, Knezevic, K, Donaldson, IJ, Green, AR, Gottgens, B. Fli1, Elf1, and Ets1 regulate the proximal promoter of the LMO2 gene in endothelial cells. Blood 2005; 106(8):2680–7.CrossRefGoogle ScholarPubMed
Wadman, IA, Osada, H, Grutz, GG, et al. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. Embo J 1997;16(11):3145–57.CrossRefGoogle ScholarPubMed
Jippo, T, Mizuno, H, Xu, Z, Nomura, S, Yamamoto, M, Kitamura, Y. Abundant expression of transcription factor GATA-2 in proliferating but not in differentiated mast cells in tissues of mice: demonstration by in situ hybridization. Blood 1996;87(3):993–8.Google Scholar
Labbaye, C, Valtieri, M, Barberi, T, et al. Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis. J Clin Invest 1995;95(5):2346–58.CrossRefGoogle ScholarPubMed
Tsai, FY, Keller, G, Kuo, FC, et al. An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 1994;371(6494):221–6.CrossRefGoogle ScholarPubMed
Nottingham, WT, Jarratt, A, Burgess, M, et al. Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer. Blood 2007;110(13):4188–97.CrossRefGoogle ScholarPubMed
Pimanda, JE, Ottersbach, K, Knezevic, K, et al. Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development. Proc Natl Acad Sci U S A 2007;104(45):17692–7.CrossRefGoogle Scholar
Wang, Q, Stacy, T, Miller, JD, et al. The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell 1996;87(4):697–708.CrossRefGoogle ScholarPubMed
Cai, Z, Bruijn, M, Ma, X, et al. Haploinsufficiency of AML1 affects the temporal and spatial generation of hematopoietic stem cells in the mouse embryo. Immunity 2000;13(4):423–31.CrossRefGoogle ScholarPubMed
Robin, C, Ottersbach, K, Durand, C, et al. An unexpected role for IL-3 in the embryonic development of hematopoietic stem cells. Dev Cell 2006;11(2):171–80.CrossRefGoogle ScholarPubMed
Huang, G, Zhang, P, Hirai, H, et al. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet 2008;40(1):51–60.CrossRefGoogle ScholarPubMed
Takahashi, K, Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126(4):663–76.CrossRefGoogle ScholarPubMed
Fisher, AG, Merkenschlager, M. Gene silencing, cell fate and nuclear organisation. Curr Opin Genet Dev 2002;12(2):193–7.CrossRefGoogle ScholarPubMed
Cao, R, Zhang, Y. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev 2004;14(2):155–64.CrossRefGoogle Scholar
Owens, BM, Hawley, RG. HOX and non-HOX homeobox genes in leukemic hematopoiesis. Stem Cells 2002;20(5):364–79.CrossRefGoogle ScholarPubMed
Kamminga, LM, Bystrykh, LV, Boer, A, et al. The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 2006;107(5):2170–9.CrossRefGoogle ScholarPubMed
Kajiume, T, Ninomiya, Y, Ishihara, H, Kanno, R, Kanno, M. Polycomb group gene mel-18 modulates the self-renewal activity and cell cycle status of hematopoietic stem cells. Exp Hematol 2004;32(6):571–8.CrossRefGoogle ScholarPubMed
Ohta, H, Sawada, A, Kim, JY, et al. Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells. J Exp Med 2002;195(6):759–70.CrossRefGoogle ScholarPubMed
Park, IK, Qian, D, Kiel, M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003;423(6937):302–5.CrossRefGoogle ScholarPubMed
Milne, TA, Briggs, SD, Brock, HW, et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell 2002;10(5):1107–17.CrossRefGoogle ScholarPubMed
Nakamura, T, Mori, T, Tada, S, et al. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell 2002; 10(5):1119–28.CrossRefGoogle ScholarPubMed
Ernst, P, Fisher, JK, Avery, W, Wade, S, Foy, D, Korsmeyer, SJ. Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell 2004;6(3):437–43.CrossRefGoogle ScholarPubMed
Rifkind, R, Bank, A, Marks, P, al. e. Fundamentals of Hematology. 2nd ed. Chicago: Year Book Medical Publishers; 1980.Google Scholar

Accessibility standard: Unknown

Accessibility compliance for the PDF of this book is currently unknown and may be updated in the future.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×