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-599cfd5f84-2stsh Total loading time: 0 Render date: 2025-01-07T07:47:39.412Z Has data issue: false hasContentIssue false

Chapter 2 - Hematopoiesis

from Section I - Developmental Hematology

Published online by Cambridge University Press:  30 January 2021

By
Amber M. D’Souza ,
Pedro A. de Alarcón  and
Mervin C. Yoder
Edited by
Pedro A. de Alarcón ,
Eric J. Werner ,
Robert D. Christensen  and
Martha C. Sola-Visner
Pedro A. de Alarcón
Affiliation:
University of Illinois College of Medicine
Eric J. Werner
Affiliation:
Children's Hospital of the King's Daughters
Robert D. Christensen
Affiliation:
University of Utah
Martha C. Sola-Visner
Affiliation:
Harvard University, Massachusetts
Get access

Summary

Hematopoiesis refers to the continuous production and release of blood cells into the circulation. As blood cells become old or injured, self-renewing hematopoietic stem cells (HSC) proliferate and differentiate to replenish multiple hematopoietic lineages. This process produces nearly 200 billion red blood cells, 10 billion white blood cells, and 400 billion platelets every day. 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.

Type
Chapter
Information
Neonatal Hematology
Pathogenesis, Diagnosis, and Management of Hematologic Problems
 , pp. 10 - 24
Publisher: Cambridge University Press
Print publication year: 2021

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.)

References

Purton, LE, Scadden, DT. Limiting factors in murine hematopoietic stem cell assays. Cell Stem Cell 2007;1:263–70.Google Scholar
Wintrobe, M. Milestones on the path of progress. In Wintrobe, M. ed. Blood, Pure, and Eloquent (New York: McGraw-Hill, 1980), p. 1.Google Scholar
Donne, A. De I-oringe des gloubles du sang, de leur mode de formation et de leur fin. C R Seances Acad Sci 1842;366–8.Google Scholar
Bizzozero, G. Uber einen Formbestandteil des Blutes und dessen Rolle bei der Thrombose und der Blutgerinnung. Virch Archiv Pathol Anat Physiol 1882; 90:261–332.Google Scholar
Jacobson, LO, Marks, EK, et al. The role of the spleen in radiation injury. Proc Soc Exp Biol Med 1949;70:740–2.Google Scholar
Ford, CE, Hamerton, JL, Barnes, DW, Loutit, JF. Cytological identification of radiation-chimaeras. Nature 1956;177:452–4.CrossRefGoogle ScholarPubMed
Becker, AJ, McCulloch, EA, Till, JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963;197:452–4.CrossRefGoogle ScholarPubMed
Pluznik, DH, Sachs, L. The cloning of normal “mast” cells in tissue culture. J Cell Physiol 1965;66:319–24.Google Scholar
Bradley, TR, Metcalf, D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci 1966;44:287–99.Google Scholar
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.Google Scholar
Spangrude, GJ. Biological and clinical aspects of hematopoietic stem cells. Annu Rev Med 1994;45:93–104.CrossRefGoogle ScholarPubMed
Harrison, . Competitive repopulation: a new assay for long-term stem cell functional capacity. Blood 1980;55:77–81.Google Scholar
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 Scholar
Orlic, D, Bodine, DM. What defines a pluripotent hematopoietic stem cell (PHSC): will the real PHSC please stand up! Blood 1994;84:3991–4.Google Scholar
Dexter, TM, Allen, TD, Lajtha, LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol 1977;91:335–44.Google Scholar
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;86:2137–45.CrossRefGoogle 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.Google Scholar
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 Scholar
Mezquita, P, Beard, BC, Kiem, H-P. NOD/SCID repopulating cells contribute only to short-term repopulation in the baboon. Gene Ther 2008;15:1460–2.Google Scholar
Park, YS, Lee, CH, Kim, JW, Shin, S, Park, CM. Differentiation of hepatocellular carcinoma from its various mimickers in liver magnetic resonance imaging: What are the tips when using hepatocyte-specific agents? World J Gastroenterol 2016;22:284–99.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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 Scholar
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.Google Scholar
Ogawa, M. Differentiation and proliferation of hematopoietic stem cells. Blood 1993;81:2844–53.Google Scholar
Watowich, SS, Wu, H, Socolovsky, M, et al. Cytokine receptor signal transduction and the control of hematopoietic cell development. Annu Rev Cell Dev Biol 1996;12:91–128.Google Scholar
Enver, T, Pera, M, Peterson, C, Andrews, PW. Stem cell states, fates, and the rules of attraction. Cell Stem Cell 2009;4:387–97.Google Scholar
Golan, K, Kumari, A, Kollet, O, et al. Daily onset of light and darkness differentially controls hematopoietic stem cell differentiation and maintenance. Cell Stem Cell 2018;23:572–85, doi:10.1016/j.stem.2018.08.002.Google Scholar
Wang, C, Cheng, L. Gankyrin as a potential therapeutic target for cancer. Invest New Drugs 2017;35 :655–6, doi:10.1007/s10637-017-0474-8.Google Scholar
Okawa, S, Nicklas, S, Zickenrott, S, Schwamborn, JC, Del Sol, AA. Generalized gene-regulatory network model of stem cell differentiation for predicting lineage specifiers. Stem Cell Rep 2016;7:307–15.Google Scholar
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.Google Scholar
Fraser, CC, Eaves, CJ, Szilvassy, SJ, Humphries, RK. Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells. Blood 1990;76:1071–6.Google Scholar
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.Google Scholar
Wineman, J, Moore, K, Lemischka, I, Müller-Sieburg, C. Functional heterogeneity of the hematopoietic microenvironment: rare stromal elements maintain long-term repopulating stem cells. Blood 1996;87:4082–90.CrossRefGoogle 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.Google Scholar
Jollie, WP. Ultrastructural studies of protein transfer across rodent yolk sac. Placenta 1986;7:263–81.Google Scholar
Zon, LI. Developmental biology of hematopoiesis. Blood 1995;86:2876–91.Google Scholar
Shalaby, F, Ho, J, Stanford, WL, et al. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997;89:981–90.Google Scholar
Choi, K, Kennedy, M, Kazarov, A, Papadimitriou, JC, Keller, G. A common precursor for hematopoietic and endothelial cells. Development 1998;125:725–32.Google Scholar
Kabrun, N, Buhring, HJ, Choi, K, et al. Flk-1 expression defines a population of early embryonic hematopoietic precursors. Development 1997;124:2039–48.Google Scholar
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
Teixeira, V, Arede, N, Gardner, R, Rodríguez-León, J, Tavares, AT. Targeting the hemangioblast with a novel cell type-specific enhancer. BMC Dev Biol 2011;11:76.Google Scholar
Serrado Marques, J, Teixeira, V, Jacinto, A Tavares, AT. Identification of novel hemangioblast genes in the early chick embryo. Cells 2018;7:9.Google Scholar
Shivdasani, RA, Orkin, SH. The transcriptional control of hematopoiesis. Blood 1996;87:4025–39.Google Scholar
Maximow, A. Relation of blood cells to connective tissues and endothelium. Physiol Rev 1924;4:533–63.Google 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.Google Scholar
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, HKA, Gekas, C, Orkin, SH, Dieterlen-Lievre, F. Placenta as a site for hematopoietic stem cell development. Exp Hematol 2005;33:1048–54.Google Scholar
Gekas, C, Dieterlen-Lièvre, F, Orkin, SH, Mikkola, HKA. The placenta is a niche for hematopoietic stem cells. Dev Cell 2005;8:365–75.Google Scholar
Müller, AM, Medvinsky, A, Strouboulis, J, Grosveld, F, Dzierzak, E. Development of hematopoietic stem cell activity in the mouse embryo. Immunity 1994;1:291–301.Google Scholar
Medvinsky, A, Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 1996;86:897–906.Google Scholar
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.Google Scholar
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.Google 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.Google Scholar
Lis, R, Karrasch, CC, Poulos, MG, et al. Conversion of adult endothelium to immunocompetent haematopoietic stem cells. Nature 2017;545:439–45.Google Scholar
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.Google Scholar
Adamo, L, Naveiras, O, Wenzel, PL, et al. Biomechanical forces promote embryonic haematopoiesis. Nature 2009;459:1131–5.Google Scholar
North, TE, Goessling, W, Peeters, M, et al. Hematopoietic stem cell development is dependent on blood flow. Cell 2009;137:736–48.Google Scholar
Diaz, MF, Li, N, Lee, HY, et al. Biomechanical forces promote blood development through prostaglandin E2 and the cAMP-PKA signaling axis. J Exp Med 2015;212:665–80.Google Scholar
Tavassoli, M. Embryonic and fetal hemopoiesis: an overview. Blood Cells 1991;17:269–81; discussion 282–6.Google Scholar
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 Scholar
Lux, CT, Yoshimoto, M, McGrath, K, et al. 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.Google Scholar
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) pp. 33–47.CrossRefGoogle 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.Google Scholar
Pereda, J, Niimi, G. Embryonic erythropoiesis in human yolk sac: two different compartments for two different processes. Microsc Res Tech 2008;71:856–62.Google Scholar
Bremer, J. The earliest blood vessels in man. Am J Anat 1914;16:447–76.Google Scholar
Pereda, J, Monge, JI, Niimi, G. Two different pathways for the transport of primitive and definitive blood cells from the yolk sac to the embryo in humans. Microsc Res Tech 2010;73:803–9.CrossRefGoogle Scholar
Freyer, C, Renfree, MB. The mammalian yolk sac placenta. J Exp Zoolog B Mol Dev Evol 2009;312:545–54.Google Scholar
Gilmour, J. Normal hematopoiesis in intra-uterine and neonatal life. J Path 1941;52:25–55.Google Scholar
Thomas, DB, Yoffey, JM. Human foetal haemopoiesis. I. The cellular composition of foetal blood. Br J Haematol 1962;8:290–5.Google Scholar
Thomas, DB, Yoffey, JM. Human foetal haematopoiesis. Ii. Hepatic haematopoiesis in the human foetus. Br J Haematol 1964;10:193–7.CrossRefGoogle ScholarPubMed
Kelemen, E, Calvo, W, Fliedner, TM. Atlas of Human Hemopoietic Development (New York: Springer-Verlag, 1979).Google Scholar
Charbord, P, Tavian, M, Humeau, L, Péault, B. Early ontogeny of the human marrow from long bones: an immunohistochemical study of hematopoiesis and its microenvironment. Blood 1996;87:4109–19.Google Scholar
Tavassoli, M. Ontogeny of hempoiesis. In Meisami, E, Timiras, P, eds. Handbook of Human Growth and Developmental Biology (Boca Raton:CRC Press, 1988), pp. 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, BC, Luevano, E, Neiman, RS. Evidence to suggest that the human fetal spleen is not a hematopoietic organ. Am J Clin Pathol 1983;80:140–4.Google 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;46:217–27.Google Scholar
Forestier, F, Daffos, F, Galacteros, F, et al. Hematological values of 163 normal fetuses between 18 and 30 weeks of gestation. Pediatr Res 1986;20:342–6.Google Scholar
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;78:51–60.Google Scholar
Porcellini, A, Manna, A, Manna, M. Ontogeny of granulocyte-macrophage progenitor cells in the human fetus. Int J Cell Cloning 1983;1:92–104.Google 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.Google Scholar
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.Google Scholar
Barclay, A Birkeland, M, Brown, M, et al. The Leucocyte Antigen Facts Book (London: Academic Press, 1993).Google Scholar
Krause, DS, Fackler, MJ, Civin, CI, May, WS. CD34: structure, biology, and clinical utility. Blood 1996;87:1–13.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
Emerson, SG. The regulation of hematopoiesis in the human fetal liver. Prog Clin Biol Res 1990;352:21–8.Google Scholar
Tavian, M, Coulombel, L, Luton, D, et al. Aorta-associated CD34+ hematopoietic cells in the early human embryo. Blood 1996;87:67–72.Google Scholar
Ivanovs, A, Rybtsov, S, Welch, L, et al. Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region. J Exp Med 2011;208:2417–27.Google Scholar
Oberlin, E, Tavian, M, Blazsek, I, Péault, B. Blood-forming potential of vascular endothelium in the human embryo. Development 2002;129:4147–57.Google Scholar
Zambidis, ET, Oberlin, E, Tavian, M, Péault, B. Blood-forming endothelium in human ontogeny: lessons from in utero development and embryonic stem cell culture. Trends Cardiovasc Med 2006;16:95–101.Google Scholar
Huyhn, A, Dommergues, M, Izac, B, et al. Characterization of hematopoietic progenitors from human yolk sacs and embryos. Blood 1995;86:4474–85.Google Scholar
Nicolini, FE, Holyoake, TL, Cashman, JD, et al. Unique differentiation programs of human fetal liver stem cells shown both in vitro and in vivo in NOD/SCID mice. Blood 1999;94:2686–95.Google Scholar
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.Google 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 (Cambridge: Cambridge Univeristy Press, 1992), pp. 155–76.Google Scholar
Kochupillai, V, Sharma, S, Sundaram, KR, Ahuja, RK. Hemopoietic improvement following fetal liver infusion in aplastic anemia. Eur J Haematol 1991;47:319–25.Google Scholar
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 Scholar
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;14:1394–1400.Google Scholar
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.Google Scholar
Sauter, C, Barker, JN. Unrelated donor umbilical cord blood transplantation for the treatment of hematologic malignancies. Curr Opin Hematol 2008;15:568–75.Google Scholar
Brunstein, CG. Umbilical cord blood transplantation for the treatment of hematologic malignancies. Cancer Control J Moffitt Cancer Cent 2011;18:222–36.Google Scholar
Chen, Y, Xu, LP, Liu, DH, et al. Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies: a single-institute analysis. Chin Med J (Engl ) 2013;126:2499–503.Google Scholar
McKinney-Freeman, SL, Daley, GQ. Towards hematopoietic reconstitution from embryonic stem cells: a sanguine future. Curr Opin Hematol 2007;14:343–7.Google Scholar
Vodyanik, MA, Slukvin, II. Hematoendothelial differentiation of human embryonic stem cells. Curr Protoc Cell Biol 2007; Chapter 23:Unit 23.6.Google Scholar
Tian, X, Woll, PS, Morris, JK, Linehan, JL, Kaufman, DS. Hematopoietic engraftment of human embryonic stem cell-derived cells is regulated by recipient innate immunity. Stem Cells 2006;24:1370–80.Google Scholar
Li, Z, Han, Z, Wu, JC. Transplantation of human embryonic stem cell-derived endothelial cells for vascular diseases. J Cell Biochem 2009;106:194–9.Google Scholar
Gomes, KMS, Costa, IC, Santos, JF, et al. Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine. Rev Assoc Med Bras(1992) 2017;63:180–9.Google Scholar
van den Hurk, M, Kenis, G, Bardy, C, et al. Transcriptional and epigenetic mechanisms of cellular reprogramming to induced pluripotency. Epigenomics 2016;8:1131–49.Google Scholar
Hu, C, Li, L. Current reprogramming systems in regenerative medicine: from somatic cells to induced pluripotent stem cells. Regen Med 2016;11:105–32.Google Scholar
Sugimura, R, Jha, DK, Han, A, et al. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature 2017;545:432–8.Google Scholar
Barcia Durán, JG, Lis, R, Lu, TM, Rafii, S. In vitro conversion of adult murine endothelial cells to hematopoietic stem cells. Nat Protoc 2018;13:2758–80.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] 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
×