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Overview of hematopoietic stem cells

Colin A Sieff, MB, BCh, FRCPath
Section Editor
Robert S Negrin, MD
Deputy Editor
Jennifer S Tirnauer, MD


The circulating blood cells are formed in bone marrow through a process called hematopoiesis. The bone marrow has an enormous production capacity; it is estimated that 1010 erythrocytes and 108 to 109 leukocytes are produced per hour in the steady state. Furthermore, while cell numbers are maintained within fairly narrow limits in normal subjects, they can be greatly amplified on demand.

These huge cell numbers are immediate descendants of maturing precursors that arise from a smaller pool of progenitors. The progenitors in turn arise from an even smaller pool of hematopoietic stem cells (HSC) that are thought to be mostly in a resting or non-dividing state and have the capacity to self-renew (and thus maintain their numbers).

HSCs are multipotent and have the capacity to differentiate into the cells of all 10 blood lineages: erythrocytes, platelets, neutrophils, eosinophils, basophils, monocytes, T and B lymphocytes, natural killer cells, and dendritic cells (figure 1) [1-3].

This topic reviews the hematopoiesis and the regulation of HSCs. A general overview of stem cells is presented separately. (See "Overview of stem cells".)


Sites of hematopoiesis — The relative red (active) marrow space of a child is much greater than that of an adult, presumably because the high requirements for red blood cell production during neonatal life. While vertebrae and pelvic bones remain active sites of hematopoiesis through life, during postnatal life red blood cell demand and therefore production is reduced, and much of the marrow space is slowly and progressively filled with fat, in particular, the marrow in the facial bones as well as the diaphyses of long bones such as the radius, ulna, femur, and fibula. Hematopoiesis becomes restricted to the skull, vertebrae, pelvis, and metaphyseal areas of long bones in adults [4]. In certain disease states that are usually associated with anemia (eg, primary myelofibrosis, infiltrative diseases of the bone marrow such as granulomas or metastatic cancer, or diseases characterized by ineffective erythropoiesis such as thalassemia major), hematopoiesis may return to its former sites in the liver, spleen, and lymph nodes and may also be found in the adrenal glands, cartilage, adipose tissue, thoracic paravertebral gutters, and even in the kidneys.


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  1. Wilson A, Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 2006; 6:93.
  2. Blank U, Karlsson G, Karlsson S. Signaling pathways governing stem-cell fate. Blood 2008; 111:492.
  3. Metcalf D. Hematopoietic cytokines. Blood 2008; 111:485.
  4. Functions of the Blood, MacFarlane RC, Robb-Smith AHT. (Eds), Blackwell Scientific, Oxford 1961. p.357.
  5. Taichman RS. Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 2005; 105:2631.
  6. Wilson A, Trumpp A. Bone marrow haematopoietic-stem-cell niches. Nature Rev Stem Cells Collection 2008; Supplement:S5.
  7. Papayannopoulou T, Scadden DT. Stem-cell ecology and stem cells in motion. Blood 2008; 111:3923.
  8. Xie Y, Yin T, Wiegraebe W, et al. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature 2009; 457:97.
  9. Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 2012; 481:457.
  10. Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 1998; 176:57.
  11. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature 2014; 505:327.
  12. Acar M, Kocherlakota KS, Murphy MM, et al. Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature 2015; 526:126.
  13. Ferraro F, Lymperi S, Méndez-Ferrer S, et al. Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci Transl Med 2011; 3:104ra101.
  14. Greenbaum A, Hsu YM, Day RB, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 2013; 495:227.
  15. Ding L, Morrison SJ. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 2013; 495:231.
  16. Omatsu Y, Sugiyama T, Kohara H, et al. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 2010; 33:387.
  17. Méndez-Ferrer S, Michurina TV, Ferraro F, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 2010; 466:829.
  18. Butler JM, Nolan DJ, Vertes EL, et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 2010; 6:251.
  19. Chow A, Lucas D, Hidalgo A, et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med 2011; 208:261.
  20. Albiero M, Poncina N, Ciciliot S, et al. Bone Marrow Macrophages Contribute to Diabetic Stem Cell Mobilopathy by Producing Oncostatin M. Diabetes 2015; 64:2957.
  21. Méndez-Ferrer S, Lucas D, Battista M, Frenette PS. Haematopoietic stem cell release is regulated by circadian oscillations. Nature 2008; 452:442.
  22. Walkley CR, Shea JM, Sims NA, et al. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell 2007; 129:1081.
  23. Walkley CR, Olsen GH, Dworkin S, et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell 2007; 129:1097.
  24. Raaijmakers MH, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 2010; 464:852.
  25. Jacobson LO, Marks EK, Gaston EO, et al. Role of the spleen in radiation injury. Proc Soc Exp Biol Med 1949; 70:7440.
  26. FORD CE, HAMERTON JL, BARNES DW, LOUTIT JF. Cytological identification of radiation-chimaeras. Nature 1956; 177:452.
  27. TILL JE, McCULLOCH EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 1961; 14:213.
  28. 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.
  29. 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.
  30. Palis J, Yoder MC. Yolk-sac hematopoiesis: the first blood cells of mouse and man. Exp Hematol 2001; 29:927.
  31. Frame JM, McGrath KE, Palis J. Erythro-myeloid progenitors: "definitive" hematopoiesis in the conceptus prior to the emergence of hematopoietic stem cells. Blood Cells Mol Dis 2013; 51:220.
  32. England SJ, McGrath KE, Frame JM, Palis J. Immature erythroblasts with extensive ex vivo self-renewal capacity emerge from the early mammalian fetus. Blood 2011; 117:2708.
  33. Medvinsky AL, Samoylina NL, Müller AM, Dzierzak EA. An early pre-liver intraembryonic source of CFU-S in the developing mouse. Nature 1993; 364:64.
  34. Medvinsky A, Dzierzak E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 1996; 86:897.
  35. Morrison SJ, White PM, Zock C, Anderson DJ. Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells. Cell 1999; 96:737.
  36. Uchida N, Buck DW, He D, et al. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 2000; 97:14720.
  37. Corey SJ, Anderson SM. Src-related protein tyrosine kinases in hematopoiesis. Blood 1999; 93:1.
  38. Fauser AA, Messner HA. Granuloerythropoietic colonies in human bone marrow, peripheral blood, and cord blood. Blood 1978; 52:1243.
  39. Fauser AA, Kanz L, Bross KJ, Löhr GW. T cells and probably B cells arise from the malignant clone in chronic myelogenous leukemia. J Clin Invest 1985; 75:1080.
  40. Fauser AA, Messner HA. Identification of megakaryocytes, macrophages, and eosinophils in colonies of human bone marrow containing neurtophilic granulocytes and erythroblasts. Blood 1979; 53:1023.
  41. Leary AG, Ogawa M, Strauss LC, Civin CI. Single cell origin of multilineage colonies in culture. Evidence that differentiation of multipotent progenitors and restriction of proliferative potential of monopotent progenitors are stochastic processes. J Clin Invest 1984; 74:2193.
  42. Nakahata T, Ogawa M. Identification in culture of a class of hemopoietic colony-forming units with extensive capability to self-renew and generate multipotential hemopoietic colonies. Proc Natl Acad Sci U S A 1982; 79:3843.
  43. Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol 1977; 91:335.
  44. Coulombel L, Kalousek DK, Eaves CJ, et al. Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. N Engl J Med 1983; 308:1493.
  45. Greenberg HM, Newburger PE, Parker LM, et al. Human granulocytes generated in continuous bone marrow culture are physiologically normal. Blood 1981; 58:724.
  46. Sutherland HJ, Lansdorp PM, Henkelman DH, et al. Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proc Natl Acad Sci U S A 1990; 87:3584.
  47. Breems DA, Blokland EA, Neben S, Ploemacher RE. Frequency analysis of human primitive haematopoietic stem cell subsets using a cobblestone area forming cell assay. Leukemia 1994; 8:1095.
  48. Bradley TR, Hodgson GS. Detection of primitive macrophage progenitor cells in mouse bone marrow. Blood 1979; 54:1446.
  49. McNiece IK, Stewart FM, Deacon DM, et al. Detection of a human CFC with a high proliferative potential. Blood 1989; 74:609.
  50. Szilvassy SJ, Humphries RK, Lansdorp PM, et al. Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy. Proc Natl Acad Sci U S A 1990; 87:8736.
  51. Kamel-Reid S, Dick JE. Engraftment of immune-deficient mice with human hematopoietic stem cells. Science 1988; 242:1706.
  52. Terstappen LW, Huang S, Safford M, et al. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. Blood 1991; 77:1218.
  53. Sutherland HJ, Eaves CJ, Eaves AC, et al. Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood 1989; 74:1563.
  54. Glimm H, Eisterer W, Lee K, et al. Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-beta2 microglobulin-null mice. J Clin Invest 2001; 107:199.
  55. Gunji Y, Nakamura M, Osawa H, et al. Human primitive hematopoietic progenitor cells are more enriched in KITlow cells than in KIThigh cells. Blood 1993; 82:3283.
  56. Kiel MJ, Yilmaz OH, Iwashita T, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005; 121:1109.
  57. Ratajczak MZ, Pletcher CH, Marlicz W, et al. CD34+, kit+, rhodamine123(low) phenotype identifies a marrow cell population highly enriched for human hematopoietic stem cells. Leukemia 1998; 12:942.
  58. Ebihara Y, Wada M, Ueda T, et al. Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+CD38- cells expressing Flk2/Flt3. Br J Haematol 2002; 119:525.
  59. Fallon P, Gentry T, Balber AE, et al. Mobilized peripheral blood SSCloALDHbr cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation. Br J Haematol 2003; 122:99.
  60. McKenzie JL, Takenaka K, Gan OI, et al. Low rhodamine 123 retention identifies long-term human hematopoietic stem cells within the Lin-CD34+CD38- population. Blood 2007; 109:543.
  61. Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 1996; 183:1797.
  62. 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.
  63. Goodell MA, Rosenzweig M, Kim H, et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 1997; 3:1337.
  64. Nakauchi H. Hematopoietic stem cells: are they CD34-positive or CD34-negative? Nat Med 1998; 4:1009.
  65. Civin CI, Almeida-Porada G, Lee MJ, et al. Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo. Blood 1996; 88:4102.
  66. Baum CM, Weissman IL, Tsukamoto AS, et al. Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci U S A 1992; 89:2804.
  67. Srour EF, Zanjani ED, Cornetta K, et al. Persistence of human multilineage, self-renewing lymphohematopoietic stem cells in chimeric sheep. Blood 1993; 82:3333.
  68. Berenson RJ, Bensinger WI, Hill RS, et al. Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. Blood 1991; 77:1717.
  69. Dunbar CE, Cottler-Fox M, O'Shaughnessy JA, et al. Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation. Blood 1995; 85:3048.
  70. Zanjani ED, Almeida-Porada G, Livingston AG, et al. Human bone marrow CD34- cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp Hematol 1998; 26:353.
  71. Bhatia M, Bonnet D, Murdoch B, et al. A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med 1998; 4:1038.
  72. Notta F, Doulatov S, Laurenti E, et al. Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science 2011; 333:218.
  73. Doulatov S, Notta F, Laurenti E, Dick JE. Hematopoiesis: a human perspective. Cell Stem Cell 2012; 10:120.
  74. Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science 1988; 241:58.
  75. Hellman S, Botnick LE, Hannon EC, Vigneulle RM. Proliferative capacity of murine hematopoietic stem cells. Proc Natl Acad Sci U S A 1978; 75:490.
  76. Ma F, Wada M, Yoshino H, et al. Development of human lymphohematopoietic stem and progenitor cells defined by expression of CD34 and CD81. Blood 2001; 97:3755.
  77. Spangrude GJ, Brooks DM, Tumas DB. Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function. Blood 1995; 85:1006.
  78. Spangrude GJ, Johnson GR. Resting and activated subsets of mouse multipotent hematopoietic stem cells. Proc Natl Acad Sci U S A 1990; 87:7433.
  79. Udomsakdi C, Eaves CJ, Sutherland HJ, Lansdorp PM. Separation of functionally distinct subpopulations of primitive human hematopoietic cells using rhodamine-123. Exp Hematol 1991; 19:338.
  80. Sun J, Ramos A, Chapman B, et al. Clonal dynamics of native haematopoiesis. Nature 2014; 514:322.
  81. Busch K, Klapproth K, Barile M, et al. Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature 2015; 518:542.
  82. Notta F, Zandi S, Takayama N, et al. Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science 2016; 351:aab2116.
  83. Kay HM. Hypothesis: How many cell-generations. Lancet 1965; 2:418.
  84. Cheshier SH, Morrison SJ, Liao X, Weissman IL. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci U S A 1999; 96:3120.
  85. Van Zant G, de Haan G, Rich IN. Alternatives to stem cell renewal from a developmental viewpoint. Exp Hematol 1997; 25:187.
  86. Harrison DE, Stone M, Astle CM. Effects of transplantation on the primitive immunohematopoietic stem cell. J Exp Med 1990; 172:431.
  87. Morrison SJ, Wandycz AM, Akashi K, et al. The aging of hematopoietic stem cells. Nat Med 1996; 2:1011.
  88. Van Zant G, Holland BP, Eldridge PW, Chen JJ. Genotype-restricted growth and aging patterns in hematopoietic stem cell populations of allophenic mice. J Exp Med 1990; 171:1547.
  89. Nijnik A, Woodbine L, Marchetti C, et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature 2007; 447:686.
  91. von Lindern M, Zauner W, Mellitzer G, et al. The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro. Blood 1999; 94:550.
  92. Jacob J, Haug JS, Raptis S, Link DC. Specific signals generated by the cytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor are not required for G-CSF-dependent granulocytic differentiation. Blood 1998; 92:353.
  93. Taya Y, Ota Y, Wilkinson AC, et al. Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation. Science 2016; 354:1152.
  94. Calvo W, Fliedner TM, Herbst E, et al. Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals. Blood 1976; 47:593.
  95. Barr RD, Whang-Peng J, Perry S. Hemopoietic stem cells in human peripheral blood. Science 1975; 190:284.
  96. Clarke BJ, Housman D. Characterization of an erythroid precursor cell of high proliferative capacity in normal human peripheral blood. Proc Natl Acad Sci U S A 1977; 74:1105.
  97. Steidl U, Kronenwett R, Rohr UP, et al. Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells. Blood 2002; 99:2037.
  98. Terskikh AV, Miyamoto T, Chang C, et al. Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood 2003; 102:94.
  99. Marley SB, Lewis JL, Gordon MY. Progenitor cells divide symmetrically to generate new colony-forming cells and clonal heterogeneity. Br J Haematol 2003; 121:643.
  100. Curry JL, Trentin JJ. Hemopoietic spleen colony studies. I. Growth and differentiation. Dev Biol 1967; 15:395.
  101. Gregory CJ, McCulloch EA, Till JE. Repressed growth of C57BL marrow in hybrid hosts reversed by antisera directed against non-H-2 alloantigens. Transplantation 1972; 13:138.
  102. Suda T, Suda J, Ogawa M. Disparate differentiation in mouse hemopoietic colonies derived from paired progenitors. Proc Natl Acad Sci U S A 1984; 81:2520.
  103. Lansdorp PM, Dragowska W. Maintenance of hematopoiesis in serum-free bone marrow cultures involves sequential recruitment of quiescent progenitors. Exp Hematol 1993; 21:1321.
  104. Shivdasani RA, Orkin SH. The transcriptional control of hematopoiesis. Blood 1996; 87:4025.
  105. Shivdasani RA. Stem cell transcription factors. Hematol Oncol Clin North Am 1997; 11:1199.
  106. Tenen DG, Hromas R, Licht JD, Zhang DE. Transcription factors, normal myeloid development, and leukemia. Blood 1997; 90:489.
  107. Metcalf D. Lineage commitment and maturation in hematopoietic cells: the case for extrinsic regulation. Blood 1998; 92:345.
  108. Enver T, Heyworth CM, Dexter TM. Do stem cells play dice? Blood 1998; 92:348.
  109. Butler JS, Dent SY. The role of chromatin modifiers in normal and malignant hematopoiesis. Blood 2013; 121:3076.
  110. Xu J, Shao Z, Glass K, et al. Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis. Dev Cell 2012; 23:796.
  111. Beerman I, Bock C, Garrison BS, et al. Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 2013; 12:413.
  112. Challen GA, Sun D, Jeong M, et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet 2011; 44:23.
  113. Kerenyi MA, Shao Z, Hsu YJ, et al. Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation. Elife 2013; 2:e00633.
  114. Stewart MH, Albert M, Sroczynska P, et al. The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal in mice. Blood 2015; 125:2075.
  115. Ghosh S, Thrasher AJ, Gaspar HB. Gene therapy for monogenic disorders of the bone marrow. Br J Haematol 2015.
  116. Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118:3132.
  117. Howe SJ, Mansour MR, Schwarzwaelder K, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest 2008; 118:3143.
  118. Stein S, Ott MG, Schultze-Strasser S, et al. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med 2010; 16:198.
  119. Boztug K, Schmidt M, Schwarzer A, et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med 2010; 363:1918.
  120. Thornhill SI, Schambach A, Howe SJ, et al. Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency. Mol Ther 2008; 16:590.
  121. Fischer A, Hacein-Bey-Abina S, Cavazzana-Calvo M. Gene therapy of primary T cell immunodeficiencies. Gene 2013; 525:170.
  122. Aiuti A, Biasco L, Scaramuzza S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 2013; 341:1233151.
  123. Chu P, Lutzko C, Stewart AK, Dubé ID. Retrovirus-mediated gene transfer into human hematopoietic stem cells. J Mol Med (Berl) 1998; 76:184.
  124. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 1978; 4:7.
  125. Schofield R. The pluripotent stem cell. Clin Haematol 1979; 8:221.
  126. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003; 425:836.
  127. Stewart FM, Crittenden RB, Lowry PA, et al. Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice. Blood 1993; 81:2566.
  128. Imanishi D, Miyazaki Y, Yamasaki R, et al. Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants. Blood 2007; 110:2231.
  129. Dezawa M, Ishikawa H, Itokazu Y, et al. Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science 2005; 309:314.
  130. Porat Y, Porozov S, Belkin D, et al. Isolation of an adult blood-derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages. Br J Haematol 2006; 135:703.
  131. Kaufman DS. Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells. Blood 2009; 114:3513.
  132. Rivière I, Dunbar CE, Sadelain M. Hematopoietic stem cell engineering at a crossroads. Blood 2012; 119:1107.
  133. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282:1145.
  134. Kaufman DS, Hanson ET, Lewis RL, et al. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 2001; 98:10716.
  135. Chadwick K, Wang L, Li L, et al. Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. Blood 2003; 102:906.
  136. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131:861.
  137. Eminli S, Foudi A, Stadtfeld M, et al. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 2009; 41:968.
  138. Hanley J, Rastegarlari G, Nathwani AC. An introduction to induced pluripotent stem cells. Br J Haematol 2010; 151:16.
  139. Park IH, Zhao R, West JA, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008; 451:141.
  140. Park IH, Lerou PH, Zhao R, et al. Generation of human-induced pluripotent stem cells. Nat Protoc 2008; 3:1180.
  141. Loh YH, Agarwal S, Park IH, et al. Generation of induced pluripotent stem cells from human blood. Blood 2009; 113:5476.
  142. Rideout WM 3rd, Hochedlinger K, Kyba M, et al. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell 2002; 109:17.
  143. Hanna J, Wernig M, Markoulaki S, et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007; 318:1920.