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2 - Hematopoiesis

from Section I - Developmental hematology

Published online by Cambridge University Press:  05 February 2013

By
Mervin C. Yoder
Edited by
Pedro de Alarcón ,
Eric Werner  and
Robert D. Christensen
Pedro de Alarcón
Affiliation:
University of Illinois College of Medicine
Eric Werner
Affiliation:
Children's Hospital of the King's Daughters
Robert D. Christensen
Affiliation:
McKay-Dee Hospital, Utah
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Summary

Hematopoiesis refers to the continuous production of circulating blood cells. From early in embryonic life to our final days on Earth, newly formed cells enter the circulation while injured, senescent, and tissue-recruited cells are withdrawn. Nearly 200 billion red blood cells, 10 billion white blood cells, and 400 billion platelets are produced daily throughout a normal lifetime. In addition to the requirement for high cell production, the concentration of individual blood cell lineages is precisely regulated in the peripheral blood and tissues. The production and use of circulating blood cells increase during periods of altered homeostasis such as defense against infection or replenishment of circulating red cells after hemorrhage. When the tightly regulated production of blood cells fails, the host may encounter life-threatening anemia or other cytopenias or suffer from excessive neoplastic growth of blood cells manifesting as leukemia.

Blood cell production is developmentally regulated and tissue specific. Blood cells are produced in several different tissues during human development, with each tissue having a characteristic pattern of blood cell production that is regulated in part by the nonhematopoietic cells in residence. This important relationship between nonhematopoietic tissue stromal elements and hematopoietic cells in regulating tissue-specific cell proliferation and differentiation is most evident during the embryonic period.

Type
Chapter
Information
Neonatal Hematology
Pathogenesis, Diagnosis, and Management of Hematologic Problems
 , pp. 11 - 24
Publisher: Cambridge University Press
Print publication year: 2013

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References

Purton, LE, Scadden, DT.Limiting factors in murine hematopoietic stem cell assays. Cell Stem Cell 2007;1:263–70.CrossRefGoogle ScholarPubMed
Wintrobe, M. Milestones on the path of progress. In: , MW, ed. Blood, Pure and Eloquent. New York: McGraw-Hill; 1980: 1.Google Scholar
Jacobson, L, Marks, E, Gaston, E, Robson, M, Zirkle, R.Role of the spleen in radiation injury. Proc Soc Exp Biol Med 1949;70:7440–2.CrossRefGoogle ScholarPubMed
Ford, C, Hamerton, J, Barnes, W, Loutit, J.Cytological identification of radiation-chimaeras. Nature 1956;177:452–4.CrossRefGoogle ScholarPubMed
Becker, A, McCulloch, E, Till, J.Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963;197:452–5.CrossRefGoogle ScholarPubMed
Pluznik, D, Sachs, L.The cloning of normal “mast” cells in tissue culture. J Cell Comp Physiol 1965;66:319–27.CrossRefGoogle ScholarPubMed
Bradley, T, Metcalf, D.The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci 1966;44:287–300.CrossRefGoogle ScholarPubMed
Stephenson, JR, Axelrad, AA, McLeod, DL, Shreeve, MM. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci USA 1971;68:1542–6.CrossRefGoogle ScholarPubMed
Spangrude, G.Biological and clinical aspects of hematopoietic stem cells. Annu Rev Med 1994;45:93–104.CrossRefGoogle ScholarPubMed
Harrison, DE. Competitive repopulation in unirradiated normal recipients. Blood 1993;81:2473–4.Google ScholarPubMed
Sutherland, HJ, Eaves, CJ, Eaves, AC, Dragowska, W, Lansdorp, PM. Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood 1989;74:1563–70.Google ScholarPubMed
Orlic, D, Bodine, D. What defines a pluripotent hematopoietic stem cell (PHSC): will the real PHSC please stand up!Blood 1994;84:3991–4.Google ScholarPubMed
Dexter, TM, Allen, TD, Lajtha, LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol 1977;91:335–44.CrossRefGoogle ScholarPubMed
Ploemacher, RE, van der Sluijs, JP, Voerman, JS, Brons, NH. An in vitro limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse. Blood 1989;74:2755–63.Google Scholar
Verfaillie, CM, Miller, JS. A novel single-cell proliferation assay shows that long-term culture-initiating cell (LTC-IC) maintenance over time results from the extensive proliferation of a small fraction of LTC-IC. Blood 1995 15;86:2137–45.Google ScholarPubMed
Zanjani, ED, Pallavicini, MG, Ascensao, JL, et al. Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero. J Clin Invest 1992;89:1178–88.CrossRefGoogle ScholarPubMed
Shultz, LD, Schweitzer, PA, Christianson, SW, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol 1995;154:180–91.Google ScholarPubMed
Mezquita, P, Beard, BC, Kiem, HP. NOD/SCID repopulating cells contribute only to short-term repopulation in the baboon. Gene Ther 2008;15:1460–2.CrossRefGoogle ScholarPubMed
Park, CY, Majeti, R, Weissman, IL. In vivo evaluation of human hematopoiesis through xenotransplantation of purified hematopoietic stem cells from umbilical cord blood. Nat Protoc 2008;3:1932–40.CrossRefGoogle ScholarPubMed
Okada, S, Harada, H, Ito, T, Saito, T, Suzu, S. Early development of human hematopoietic and acquired immune systems in new born NOD/Scid/Jak3null mice intrahepatic engrafted with cord blood-derived CD34 + cells. Int J Hematol 2008;88:476–82.CrossRefGoogle ScholarPubMed
Traggiai, E, Chicha, L, Mazzucchelli, L, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 2004;304:104–7.CrossRefGoogle ScholarPubMed
Ishikawa, F, Yasukawa, M, Lyons, B, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood 2005;106:1565–73.CrossRefGoogle ScholarPubMed
Bradford, GB, Williams, B, Rossi, R, Bertoncello, I. Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp Hematol 1997;25:445–53.Google ScholarPubMed
Foudi, A, Hochedlinger, K, Van Buren, D, et al. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol 2009;27:84–90.CrossRefGoogle ScholarPubMed
Ogawa, M.Differentiation and proliferation of hematopoietic stem cells. Blood 1993;81:2844–53.Google ScholarPubMed
Metcalf, D.Hematopoietic regulators: redundancy or subtlety?Blood 1993;82:3515–23.Google ScholarPubMed
Watowich, SS, Wu, H, Socolovsky, M, Klingmuller, U, Constantinescu, SN, Lodish, HF. Cytokine receptor signal transduction and the control of hematopoietic cell development. Annu Rev Cell Dev Biol 1996;12:91–128.CrossRefGoogle ScholarPubMed
Enver, T, Pera, M, Peterson, C, Andrews, PW. Stem cell states, fates, and the rules of attraction. Cell Stem Cell 2009;4:387–97.CrossRefGoogle ScholarPubMed
Osawa, M, Hanada, K, Hamada, H, Nakauchi, H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996;273:242–5.CrossRefGoogle ScholarPubMed
Kent, DG, Copley, MR, Benz, C, et al. Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential. Blood 2009;113:6342–50.CrossRefGoogle ScholarPubMed
Fraser, CC, Eaves, CJ, Szilvassy, SJ, Humphries, RK. Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells. Blood 1990;76:1071–6.Google ScholarPubMed
Miller, CL, Eaves, CJ. Expansion in vitro of adult murine hematopoietic stem cells with transplantable lympho-myeloid reconstituting ability. Proc Natl Acad Sci USA 1997;94:13648–53.CrossRefGoogle ScholarPubMed
Wineman, J, Moore, K, Lemischka, I, Muller-Sieburg, C.Functional heterogeneity of the hematopoietic microenvironment: rare stromal elements maintain long-term repopulating stem cells. Blood 1996;87:4082–90.Google ScholarPubMed
Bowie, MB, Kent, DG, Copley, MR, Eaves, CJ. Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells. Blood 2007;109:5043–8.CrossRefGoogle ScholarPubMed
Jollie, W. Ultrastructural studies of protein transfer across rodent yolk sac. Placenta 1986;7:263–81.CrossRefGoogle ScholarPubMed
Zon, L.Developmental biology of hematopoiesis. Blood 1995;86:2876–91.Google ScholarPubMed
Shalaby, F, Ho, J, Stanford, WL, et al. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997;89:981–90.CrossRefGoogle ScholarPubMed
Choi, K, Kennedy, M, Kazarov, A, Papadimitriou, JC, Keller, G.A common precursor for hematopoietic and endothelial cells. Development 1998;125:725–32.Google ScholarPubMed
Kabrun, N, Buhring, HJ, Choi, K, Ullrich, A, Risau, W, Keller, G. Flk-1 expression defines a population of early embryonic hematopoietic precursors. Development 1997;124:2039–48.Google 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;432:625–30.CrossRefGoogle ScholarPubMed
Shivdasani, R, Orkin, S. The transcriptional control of hematopoiesis. Blood 1996;87:4025–39.Google ScholarPubMed
Maximow, AA. Relation of blood cells to connective tissues and endothelium. Physiol Rev 1924;4:533–63.CrossRefGoogle Scholar
Rhodes, KE, Gekas, C, Wang, Y, et al. The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell Stem Cell 2008;2:252–63.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;18:279–96.CrossRefGoogle ScholarPubMed
Samokhvalov, IM, Samokhvalova, NI, Nishikawa, S. Cell tracing shows the contribution of the yolk sac to adult haematopoiesis. Nature 2007;446:1056–61.CrossRefGoogle ScholarPubMed
Mikkola, HK, Gekas, C, Orkin, SH, Dieterlen-Lievre, F.Placenta as a site for hematopoietic stem cell development. Exp Hematol 2005;33:1048–54.CrossRefGoogle ScholarPubMed
Gekas, C, Dieterlen-Lievre, F, Orkin, SH, Mikkola, HK. The placenta is a niche for hematopoietic stem cells. Dev Cell 2005;8:365–75.CrossRefGoogle ScholarPubMed
Muller, AM, Medvinsky, A, Strouboulis, J, Grosveld, F, Dzierzak, E. Development of hematopoietic stem cell activity in the mouse embryo. Immunity 1994;1:291–301.CrossRefGoogle ScholarPubMed
Medvinsky, A, Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 1996;86:897–906.CrossRefGoogle ScholarPubMed
Cumano, A, Dieterlen-Lievre, F, Godin, I.Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 1996;86:907–16.CrossRefGoogle ScholarPubMed
Chen, MJ, Yokomizo, T, Zeigler, BM, Dzierzak, E, Speck, NA. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature 2009;457:887–91.CrossRefGoogle Scholar
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 USA 2005;102:134–9.CrossRefGoogle ScholarPubMed
Zovein, AC, Hofmann, JJ, Lynch, M, et al. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 2008;3:625–36.CrossRefGoogle ScholarPubMed
Adamo, L, Naveiras, O, Wenzel, PL, et al. Biomechanical forces promote embryonic haematopoiesis. Nature 2009;459:1131–5.CrossRefGoogle ScholarPubMed
North, TE, Goessling, W, Peeters, M, et al. Hematopoietic stem cell development is dependent on blood flow. Cell 2009;137:736–48.CrossRefGoogle ScholarPubMed
Tavassoli, M.Embryonic and fetal hemopoiesis: an overview. Blood Cells 1991;17:269–81; discussion 82–6.Google ScholarPubMed
Rich, IN. The developmental biology of hemopoiesis: effect of growth factors on the colony formation by embryonic cells. Exp Hematol 1992;20:368–70.Google ScholarPubMed
Lux, CT, Yoshimoto, M, McGrath, K, Conway, SJ, Palis, J, Yoder, MC. All primitive and definitive hematopoietic progenitor cells emerging before E10 in the mouse embryo are products of the yolk sac. Blood 2008;111:3435–8.CrossRefGoogle ScholarPubMed
Enders, A, King, B. Development of the human yolk sac. In: Nogales, F, ed. The Human Yolk Sac and Yolk Sac tumors. Berlin: Springer-Verlag; 1993: 33–47.Google Scholar
Brent, RL, Beckman, DA, Jensen, M, Koszalka, TR. Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis. Teratology 1990;41:405–13.CrossRefGoogle ScholarPubMed
Pereda, J, Niimi, G. Embryonic erythropoiesis in human yolk sac: two different compartments for two different processes. Microsc Res Tech 2008;71:856–62.CrossRefGoogle ScholarPubMed
Bremer, J.The earliest blood vessels in man. Am J Anat 1914;16:447–76.CrossRefGoogle Scholar
Freyer, C, Renfree, MB. The mammalian yolk sac placenta. J Exp Zool B Mol Dev Evol 2009;312:545–54.CrossRefGoogle ScholarPubMed
Gilmour, J.Normal hematopoiesis in intra-uterine and neonatal life. J Path 1941;52:25–55.CrossRefGoogle Scholar
Thomas, DB, Yoffey, JM. Human foetal haematopoiesis. II. Hepatic haematopoiesis in the human foetus. Br J Haematol 1964;10:193–7.CrossRefGoogle ScholarPubMed
Thomas, DB, Yoffey, JM. Human foetal haematopoiesis. I. The cellular composition of foetal blood. Br J Haematol 1962;8:290–5.CrossRefGoogle ScholarPubMed
Kelemen, E, Calvo, W, Fleidner, TM. Atlas of Human Hemopoietic Development. New York: Springer-Verlag, 1979.CrossRefGoogle Scholar
Charbord, P, Tavian, M, Humeau, L, Peault, B. Early ontogeny of the human marrow from long bones: An immunohistochemical study of hematopoiesis and its microenvironment. Blood 1996;87:4109–19.Google ScholarPubMed
Tavassoli, M. Ontogeny of hemopoiesis. In: Meisami, E, Timiras, P, eds. Handbook of Human Growth and Developmental Biology. Boca Raton: CRC Press; 1988; 101–12.Google Scholar
Kelemen, E, Gulya, E, Vass, K. Ontogeny of human neutrophil granulocyte alkaline phosphatase. J Cell Physiol 1978;95:353–4.CrossRefGoogle ScholarPubMed
Wolf, B, Luevano, E, Neiman, R. Evidence to suggest that the human fetal spleen is not a hematopoietic organ. Am J Clin Pathol 1983;80:140–4.CrossRefGoogle Scholar
Calhoun, DA, Li, Y, Braylan, RC, Christensen, RD. Assessment of the contribution of the spleen to granulocytopoiesis and erythropoiesis of the mid-gestation human fetus. Early Hum Dev 1996;46(3):217–27.CrossRefGoogle ScholarPubMed
Forestier, F, Daffos, F, Galacteros, F, Bardakjian, J, Rainaut, M, Beuzard, Y.Hematological values of 163 normal fetuses between 18 and 30 weeks of gestation. Pediatr Res 1986;20(4):342–6.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
Procellini, A, Manna, A, Manna, M. Ontogeny of granulocyte-macrophage progenitor cells in the human fetus. Int J Cell Cloning 1983;1:92–104.CrossRefGoogle Scholar
Peschle, C, Migliaccio, AR, Migliaccio, G, et al. Embryonic–fetal Hb switch in humans: studies on erythroid bursts generated by embryonic progenitors from yolk sac and liver. Proc Natl Acad Sci USA 1984;81:2416–20.CrossRefGoogle ScholarPubMed
Barclay, A, Birkeland, M, Brown, M, et al. The Leucocyte Antigen Facts Book. London: Academic Press; 1993.Google Scholar
Krause, D, Fackler, M, Civin, C, May, W.CD34: Structure, biology, and clinical utility. Blood 1996;87:1–13.Google ScholarPubMed
Gilles, JM, Divon, MY, Bentolila, E, et al. Immunophenotypic characterization of human fetal liver hematopoietic stem cells during the midtrimester of gestation. Am J Obstet Gynecol 1997;177:619–25.CrossRefGoogle ScholarPubMed
Muench, MO, Roncarolo, MG, Namikawa, R. Phenotypic and functional evidence for the expression of CD4 by hematopoietic stem cells isolated from human fetal liver. Blood 1997;89:1364–75.Google ScholarPubMed
Emerson, SG.The regulation of hematopoiesis in the human fetal liver. Prog Clin Biol Res 1990;352:21–8.Google 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;87:67–72.Google ScholarPubMed
Oberlin, E, Tavian, M, Blazsek, I, Peault, B.Blood-forming potential of vascular endothelium in the human embryo. Development 2002;129:4147–57.Google ScholarPubMed
Zambidis, ET, Oberlin, E, Tavian, M, Peault, B.Blood-forming endothelium in human ontogeny: lessons from in utero development and embryonic stem cell culture. Trends Cardiovasc Med 2006;16:95–101.CrossRefGoogle ScholarPubMed
Huyhn, A, Dommergues, M, Izac, B, et al. Characterization of hematopoietic progenitors from human yolk sacs and embryos. Blood 1995;86:4474–85.Google ScholarPubMed
Harrison, J, Kappas, A, Levere, RD, et al. Additive effect of erythropoietin and heme on murine hematopoietic recovery after azidothymidine treatment. Blood 1993;82:3574–9.Google ScholarPubMed
Zanjani, ED, Flake, AW, Rice, H, Hedrick, M, Tavassoli, M. Long-term repopulating ability of xenogeneic transplanted human fetal liver hematopoietic stem cells in sheep. J Clin Invest 1994;93:1051–5.CrossRefGoogle Scholar
Touraine, J. Transplantation of fetal hematopoietic and lymphopoietic cells in humans, with special reference to in utero transplantation. In: Edwards, R, ed. Fetal Tissue Transplants in Medicine. 1st edn. Cambridge: University Press, Cambridge; 1992: 155–76.Google Scholar
Kochupillai, V, Sharma, S, Sundaram, K, Ahuja, R.Hematopoietic improvement following fetal liver infusion in aplastic anemia. Eur J Haematol 1991;47:319–25.CrossRefGoogle ScholarPubMed
Turner, CW, Yeager, AM, Waller, EK, Wingard, JR, Fleming, WH. Engraftment potential of different sources of human hematopoietic progenitor cells in BNX Mice. Blood 1996;87:3237–44.Google ScholarPubMed
Kumar, P, Defor, TE, Brunstein, C, et al. Allogeneic hematopoietic stem cell transplantation in adult acute lymphocytic leukemia: impact of donor source on survival. Biol Blood Marrow Transplant 2008;14:1394–400.CrossRefGoogle ScholarPubMed
Atsuta, Y, Suzuki, R, Nagamura-Inoue, T, et al. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. Blood 2009;113:1631–8.CrossRefGoogle ScholarPubMed
Sauter, C, Barker, JN. Unrelated donor umbilical cord blood transplantation for the treatment of hematologic malignancies. Curr Opin Hematol 2008;15:568–75.CrossRefGoogle ScholarPubMed
McKinney-Freeman, SL, Daley, GQ. Towards hematopoietic reconstitution from embryonic stem cells: a sanguine future. Curr Opin Hematol 2007;14:343–7.CrossRefGoogle ScholarPubMed
Vodyanik, MA, Slukvin, II. Hematoendothelial differentiation of human embryonic stem cells. Curr Protoc Cell Biol 2007; Chapter 23: Unit 23 6.CrossRefGoogle ScholarPubMed
Muller, LU, Daley, GQ, Williams, DA. Upping the ante: recent advances in direct reprogramming. Mol Ther 2009;17:947–53.CrossRefGoogle ScholarPubMed
Ohnuki, M, Takahashi, K, Yamanaka, S. Generation and characterization of human induced pluripotent stem cells. Curr Protoc Stem Cell Biol 2009; Chapter 4: Unit 4A2.CrossRefGoogle ScholarPubMed
Lindop, PJ, Rotblat, J. The age factor in the susceptibility of man and animals to radiation. I. The age factor in radiation sensitivity in mice. Br J Radiol 1962;35:23–31.CrossRefGoogle ScholarPubMed
Zwiebel, JA, Bano, M, Nexo, E, Salomon, DS, Kidwell, WR. Partial purification of transforming growth factors from human milk. Cancer Res 1986;46:933–9.Google ScholarPubMed

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