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Molecular Biology of Erythropoiesis

  • James Palis

Abstract

Red cells, comprising the most abundant cell type in the body, are uniquely designed to withstand the vicissitudes of the microcirculation to deliver oxygen to the tissues. Red cells are produced in the bone marrow where they undergo progressive maturation from unilineage progenitors to morphologically defined precursors to enucleated erythrocytes. Two distinct erythroid lineages exist during mammalian ontogeny. The first “primitive” erythroid lineage originates during early embryogenesis in the yolk sac and generates a transient wave of maturing erythroid cells. The second “definitive” erythroid lineage exists in the fetus and throughout postnatal life. Erythropoietin is the primary cytokine regulating erythroid cell maturation by signaling through its receptor to activate multiple intracellular signaling cascades. Erythropoiesis is also regulated by transcriptional complexes containing GATA-1, SCL, EKLF, and multiple other factors. These complexes assist in the creation of transcriptionally active chromatin regions and upregulate erythroid-specific genes. MicroRNAs have recently been found in erythroid cells and raise the possibility that gene downregulation is also important for lineage maturation. A better understanding of the regulation of the globin genes expressed in the embryo, fetus, and adult will ultimately lead to improved therapies for people with hemoglobinopathies, including sickle cell disease and thalassemia.

Keywords

Stem Cell Factor Globin Gene Erythroid Cell Erythroid Progenitor Erythroid Differentiation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Allen, T. D., and Dexter, T. M. 1984. The essential cells of the hematopoietic microenvironment. Exp Hematol 12:517–521.PubMedGoogle Scholar
  2. Amstrong, J. A., Bieker, J. J., and Emerson, B. M. 1998. A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue-specific transcriptional regulation by EKLF in vitro. Cell 95:93–104.Google Scholar
  3. Anderson, K. P., Crable, S. C., and Lingrel, J. B. 2000. The GATA-E box-GATA motif in the EKLF promoter is required for in vivo expression. Blood 95:1652–1655.PubMedGoogle Scholar
  4. Arcasoy, M. O., and Jiang, X. 2005. Co-operative signalling mechanisms required for erythroid precursor expansion in response to erythropoietin and stem cell factor. Br J Haematol 130:121–129.PubMedGoogle Scholar
  5. Basu, P., Morris P. E., Haar J. L., Wani, M. A., Lingrel, J. B., Gaensler, K. M., and Lloyd, J. A. 2005. KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic beta-like globin genes in vivo. Blood 106:2566–2571.PubMedGoogle Scholar
  6. Begley, C. G., Aplan, P. D., Denning, S. M., Haynes, B. F., Waldmann, T. A., and Kirsch, I. R. 1989. The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif. Proc Natl Acad Sci USA 86:10128–10132.PubMedGoogle Scholar
  7. Bender, M. A., Bulger, M., Close, J., and Groudine, M. 2000. Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region. Mol Cell 5:387–393.PubMedGoogle Scholar
  8. Bessis, M., Mize, C., and Prenant, M. 1978. Erythropoiesis: Comparison of in vivo and in vitro amplification. Blood Cells 4:155–174.PubMedGoogle Scholar
  9. Bethlenfalvay, N. C., and Block, M. 1970. Fetal erythropoiesis. Maturation in megaloblastic yolk sac. erythropoiesis in the C57Bl/6J mouse. Acta Haematol 44:240–245.Google Scholar
  10. Blobel, G. A., Nakajima, T., Eckner, R., Montminy, M., and Orkin, S. H. 1998. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation. Proc Natl Acad Sci USA 95:2061–2066.PubMedGoogle Scholar
  11. Boas, F. E., Forman, L., and Beutler, E. 1998. Phosphatidylserine exposure and red cell viability in red cell aging and in hemolytic anemia. Proc Natl Acad Sci USA 95:3077–3081.PubMedGoogle Scholar
  12. Broudy, V. C. 1997. Stem cell factor and hematopoiesis. Blood 90:1345–1364.PubMedGoogle Scholar
  13. Broudy, V. C., Lin, N. L., Priestley, G. V., Nocka, K., and Wolf, N. S. 1996. Interaction of stem cell factor and its receptor c-kit mediates lodgment and acute expansion of hematopoietic cells in the murine spleen. Blood 88:75–81.PubMedGoogle Scholar
  14. Bulger, M., Schubeler, D., Bender, M. A., Hamilton, J., Farrell, C. M., Hardison, R. C., and Groudine, M. 2003. A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse beta-globin locus. Mol Cell Biol 23:5234–5244.PubMedGoogle Scholar
  15. Chasis, J. A., Prenant, M., Leung, A., and Mohandas, N. 1989. Membrane assembly and remodeling during reticulocyte maturation. Blood 74:1112–1120.PubMedGoogle Scholar
  16. Chin, H., Arai, A., Wakao, H., Kamiyama, R., Miyasaka, N., and Miura, O. 1998. Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway. Blood 91:3734–3745.PubMedGoogle Scholar
  17. Choong, M. L., Yang, H. H., and McNiece, I. 2007. MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis. Exp Hematol 35:551–564.PubMedGoogle Scholar
  18. Dai, C. H., Krantz, S. B., and Zsebo, K. M. 1991. Human burst-forming units – erythroid need direct interaction with stem cell factor for further development. Blood 78:2493–2497.PubMedGoogle Scholar
  19. de la Chapelle, A., Fantoni, A., and Marks, P. 1969. Differentiation of mammalian somatic cells: DNA and hemoglobin synthesis in fetal mouse yolk sac erythroid cells . Proc Natl Acad Sci USA 63:812–819.PubMedGoogle Scholar
  20. de Maria, R., Testa, U., Luchetti, L., Zeuner, A., Stassi, G., Pelosi, E., Riccioni, R., Felli, N., Samoggia, P., and Peschle, C. 1999. Apoptotic role of Fas/Fas ligand system in the regulation of erythropoiesis. Blood 93:796–803.PubMedGoogle Scholar
  21. Dore, L. C., Amigo, J. D., Dos Santos, C. O., Zhang, Z., Gai, X., Tobias, J. W., Yu, D., Klein, A. M., Dorman, C., Wu, W., Hardison, R. C., Paw, B. H., and Weiss, M. J. 2008. A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci USA 105:3333–3338.PubMedGoogle Scholar
  22. Emerson, S. G., Shanti, T., Ferrara, J. L., and Greenstein, J. L. 1989. Developmental regulation of erythropoiesis by hematopoietic growth factors: Analysis on populations of BFU-E from bone marrow, peripheral blood, and fetal liver. Blood 74:49–55.PubMedGoogle Scholar
  23. Enver, T., Raich, N, Ebens, A. J., Papayannopoulou, T., Costantini, F., and Stamatoyannopoulos, G. 1990. Developmental regulation of human fetal-to-adult globin gene switching in trans-genic mice. Nature 344:309–313.PubMedGoogle Scholar
  24. Erslev, A. J. and Besarab, A. 1997. Erythropoietin in the pathogenesis and treatment of the anemia of chronic renal failure. Kidney Int 51:622–630.PubMedGoogle Scholar
  25. Fader, C. M., and Colombo, M. I. 2006. Multivesicular bodies and autophagy in erythrocyte maturation. Autophagy 2:122–125.PubMedGoogle Scholar
  26. Ferkowicz, M. J., and Yoder, M. C. 2005. Blood island formation: Longstanding observations and modern interpretations. Exp Hematol 33:1041–1047.PubMedGoogle Scholar
  27. Fraser, S., Isern, J., and Baron, M. 2007. Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell surface antigen expression . Blood 109:343–352.PubMedGoogle Scholar
  28. Fujiwara, Y., Browne, C. P., Cunniff, K., Goff, S. C., and Orkin, S. H. 1996. Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1 . Proc Natl Acad Sci USA 93:12355–12358.PubMedGoogle Scholar
  29. Gaiduschek J. B., and Singer, S. J. 1979. Molecular changes in the membranes of mouse erythroid cells accompanying differentiation. Cell 16:149–163.Google Scholar
  30. Gardiner, M. R., Gongora, M. M., Grimmond, S. M., and Perkins, A. C. 2007. A global role for zebrafish klf4 in embryonic erythropoiesis. Mech Dev 124:762–774.PubMedGoogle Scholar
  31. Gifford, S. C., Derganc, J., Shevkoplyas, S. S., Yoshida, T., Bitensky, M. W. 2006. A detailed study of time-dependent changes in human red blood cells: From reticulocyte maturation to erythrocyte senescence. Br J Haematol 135: 395–404.PubMedGoogle Scholar
  32. Gulliver, G. 1875. Observations on the sizes and shapes of red corpuscles of the blood of vertebrates, with drawings of them to a uniform scale, and extended and revised tables of measurements. Proc Zool Soc London 474–495.Google Scholar
  33. Hall, M. A., Curtis, D. J., Metcalf D., Elefanty, A. G., Sourris, K., Robb , L. , Gothert , J. R. , Jane , S. M. , and Begley , C. G. 2003. The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12. Proc Natl Acad Sci USA 100:992–997.PubMedGoogle Scholar
  34. Hanspal, M., and Hanspal, J. S. 1994. The association of erythroblasts with macrophages promotes erythroid proliferation and maturation: A 30-kD heparin-binding protein is involved in this contact. Blood 84:3494–3504.PubMedGoogle Scholar
  35. Hanspal, M., Smockova, Y., and Uong, Q. 1998. Molecular identification and functional characterization of a novel protein that mediates the attachment of erythroblasts to macrophages . Blood 92:2940–2950.PubMedGoogle Scholar
  36. Harju, S., McQueen, K. J., and Peterson, K. R. 2002. Chromatin structure and control of beta-like globin gene switching. Exp Biol Med 227:683–700.Google Scholar
  37. Heath, D. S., Axelrod, A. A., McLeod, D. L., and Shreeve, M. M. 1976. Separation of the eryth-ropoietin-responsive BFU-E and CFU-E in mouse bone marrow by unit gravity separation . Blood 47:777–792.PubMedGoogle Scholar
  38. Hodge, D., Coghill, E., Keys, J., Maguire, T., Hartmann, B., McDowall, A., Weiss, M., Grimmond, S., and Perkins, A. 2006. A global role for EKLF in definitive and primitive erythropoiesis. Blood 107:3359–3370.PubMedGoogle Scholar
  39. Ingley, E., McCarthy, D. J., Pore, J. R., Sarna, M. K., Adenan, A. S., Wright, M. J., Erber, W., Tilbrook, P. A., and Klinken, S. P. 2005. Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis. Oncogene 24:336–343.PubMedGoogle Scholar
  40. Iscove, N. N. 1977. The role of erythropoietin in regulation of population size and cell cycling of early and late erythroid precursors in mouse bone marrow. Cell Tissue Kinet 10:323–334.PubMedGoogle Scholar
  41. Jaakkola, P., Mole, D. R., Tian, Y. M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, Av., Hebestreit, H. F., Mukherji, M., Schofield, C. J., Maxwell, P. H., Pugh, C. W., and Ratcliffe, P. J. 2001. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468–472.PubMedGoogle Scholar
  42. Ji, R. P., Phoon, C. K. L., Aristizäbal, O., McGrath, K. E., Palis, J., and Turnbull, D. H. 2003. Onset of cardiac function during early mouse embryogenesis coincides with entry of primitive erythroblasts into the embryo proper. Circ Res 92:133–135.PubMedGoogle Scholar
  43. Ji, P., Jayapal, S. R., and Lodish, H. F. 2008. Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2. Nat Cell Biol 10:314–321.PubMedGoogle Scholar
  44. Johnson, G. R., and Moore, M. A. S. 1975. Role of stem cell migration in initiation of mouse foetal liver haemopoiesis. Nature 258:726–728.PubMedGoogle Scholar
  45. Johnstone, R. M., Mathew, A., Mason, A. B., and Teng, K. 1991. Exosome formation during maturation of mammalian and avian reticulocytes: Evidence that exosome release is a major route for externalization of obsolete membrane proteins. J Cell Physiol 147:27–36.PubMedGoogle Scholar
  46. Kapur, R., and Zhang, L. 2001. A novel mechanism of cooperation between c-Kit and erythropoietin receptor. Stem cell factor induces the expression of Stat5 and erythropoietin receptor, resulting in efficient proliferation and survival by erythropoietin. J Biol Chem 276:1099–1106.Google Scholar
  47. Kawane, K., Fukuyama, H., Kondoh, G., Takeda, J., Ohsawa, Y., Uchiyama, Y., and Nagata, S. 2001. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver . Science 292:1546–1549.PubMedGoogle Scholar
  48. Khandelwal, S., van Rooijen, N., and Saxena, R. K. 2007. Reduced expression of CD47 during murine red blood cell RBC. senescence and its role in RBC clearance from the circulation . Transfusion 7:1725–1732.Google Scholar
  49. Kieran, M. W., Perkins, A. C., Orkin, S. H., and Zon, L. Z. 1996. Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor . Proc Natl Acad Sci USA 93:9126–9131.PubMedGoogle Scholar
  50. Kingsley, P. D., Malik, J., Fantauzzo, K., and Palis, J. 2004. Yolk sac-derived primitive erythrob-lasts enucleate during mammalian embryogenesis. Blood 104:19–25.PubMedGoogle Scholar
  51. Kingsley, P. D., Malik, J., Emerson, R. L., Bushnell, T. P., McGrath, K. E., Bloedorn, L. A., Bulger, M., Palis, J. 2006. “Maturational” globin switching in primary primitive erythroid cells. Blood 104:1665–1672.Google Scholar
  52. Knoll, W. 1927. Blut und blutbildende organe menschlicher embryonen. Schriften der Schweizerischen Naturforschenden Gesellschaft 64:1–81.Google Scholar
  53. Koury, M. J., and Bondurant, M. C. 1990. Erythropoietin retards DNA breakdown and prevents programmed cell death in erythroid progenitor cells. Science 248:378–381.PubMedGoogle Scholar
  54. Koury, S. T., Koury, M. J., and Bondurant, M. C. 1989. Cytoskeletal distribution and function during the maturation and enucleation of mammalian erythroblasts. J Cell Biol 109:3005–3013.PubMedGoogle Scholar
  55. Kunisaki, Y., Masuko, S., Noda, M., Inayoshi, A., Sanui, T., Harada, M., Sasazuki, T., and Fukui, Y. 2004. Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phos-phatidylserine receptor. Blood 103:3362–3364.PubMedGoogle Scholar
  56. Kurata, H., Mancini, G. C., Alespieti, G., Migliaccio, A. R., and Migliaccio, G. 1998. Stem cell factor induces proliferation and differentiation of fetal progenitor cells in the mouse . Br J Haematol 101:676–687.PubMedGoogle Scholar
  57. Lee, J. C., Gimm, J. A., Lo, A. J., Koury, M. J., Krauss, S. W., Mohandas, N., and Chasis, J. A. 2004. Mechanism of protein sorting during erythroblast enucleation: Role of cytoskeletal connectivity. Blood 103:1912–1919.PubMedGoogle Scholar
  58. Lee, G., Lo, A., Short, S. A., Mankelow, T. J., Spring, F., Parsons, S. F., Yazdanbakhsh, K., Mohandas, N., Anstee, D. J., and Chasis, J. A. 2006. Targeted gene deletion demonstrates that the cell adhesion molecule ICAM-4 is critical for erythroblastic island formation . Blood 108:2064–2071.PubMedGoogle Scholar
  59. Letting, D. L., Rakowski, C., Weiss, M. J., Blobel, G. A. 2003. Formation of a tissue-specific histone acetylation pattern by the hematopoietic transcription factor GATA-1 . Mol Cell Biol 23:1334–1340.PubMedGoogle Scholar
  60. Lin, C.-S., Lim, S.-K., D'Agati, V., and Constantini, F. 1996. Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis . Genes Dev 10 : 154 – 164 .PubMedGoogle Scholar
  61. Lux, C. T., Yoshimoto, M., McGrath, K., Conway, S. J., Palis, J., and Yoder, M. C. 2008. All primitive and definitive hematopoietic progenitor cells emerging prior to E10 in the mouse embryo are products of the yolk sac. Blood, in press.Google Scholar
  62. Maximow, A. A. 1909. Untersuchungen uber blut und bindegewebe 1. Die fruhesten entwick-lungsstadien der blut- und binde- gewebszellan bein saugetierembryo, bis zum anfang der blutbilding unden leber. Arch Mikroskop Anat. 73:444–561.Google Scholar
  63. Maxwell, P. H., Wiesener, M. S., Chang, G. W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., and Ratcliffe, P. J. 1999. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275.PubMedGoogle Scholar
  64. McGrath, K. E., Koniski, A. D., Malik, J., and Palis, J. 2003. Circulation is established in a step-wise pattern in the mammalian embryo. Blood 101:1669–1676.PubMedGoogle Scholar
  65. McGrath, K. E., Kingsley, P. D., Koniski, A. D., Porter, R. L., Bushnell, T. P., and Palis, J. 2008. Enucleation of primitive erythroid cells generates a transient population of “pyrenocytes” in the mammalian fetus. Blood 111:2409–2417.PubMedGoogle Scholar
  66. McNiece, I. K., Langley, K. E., and Zsebo, K. M. 1991. Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and EPO to stimulate human progenitor cells of the myeloid and erythroid lineages. Exp Hematol 19:226–231.PubMedGoogle Scholar
  67. Meier, N., Krpic, S., Rodriguez, P., Strouboulis, J., Monti, M., Krijgsveld, J., Gering, M., Patient, R., Hostert, A., and Grosveld, F. 2006. Novel binding partners of Ldb1 are required for haematopoietic development. Development 133:4913–4924.PubMedGoogle Scholar
  68. Meyron-Holz, E. G., Fibach, E., Gelvan, D., and Konijn, A. M. 1994. Binding and uptake of exogenous isoferritins by cultured human erythroid precursor cells . Br J Haematol 86:635–641.Google Scholar
  69. Migliaccio , A. R. and Migliaccio , G. 1988. Human embryonic hemopoiesis: Control mechanisms underlying progenitor differentiation in vitro. Dev Biol 125:127–134.PubMedGoogle Scholar
  70. Miller, I. J., and Bieker, J. J. 1993. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins. Mol Cell Biol 13:2776–2786.PubMedGoogle Scholar
  71. Mohandas, N. and Prenant M. 1978. Three-dimensional model of bone marrow. Blood 51:633–643.PubMedGoogle Scholar
  72. Motoyama, N., Kimura, T., Takahashi, T., Watanabe, T., and Nakano, T. 1999. bcl-x prevents apoptotic cell death of both primitive and definitive erythrocytes at the end of maturation . J Exp Med 11:1691–1698.Google Scholar
  73. Muta, K., Krantz, S. B., Bondurant, M. C., and Dai, C. H. 1995. Stem cell factor retards differentiation of normal human erythroid progenitor cells while stimulating proliferation. Blood 86:572–580.PubMedGoogle Scholar
  74. Nemenman, I., Escola, G. S., Hlavacek, W. S., Unkefer, P. J., Unkefer, C. J., and Wall, M. E. 2007. Reconstruction of metabolic networks from high-throughput metabolite profiling data: In sil-ico analysis of red blood cell metabolism. 2007. Ann N Y Acad Sci 1115:102–115.Google Scholar
  75. Neubauer, H., Cumano, A., Müller, M., Wu, H., Huffstadt, U., and Pfeffer, K. 1998. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 93:397–409.PubMedGoogle Scholar
  76. Nichols, K. E., Crispino, J. D., Poncz, M., White, J. G., Orkin, S. H., Maris, J. M., and Weiss, M. J. 2000. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet 24:266–270.PubMedGoogle Scholar
  77. Nuez, B., Michalovich, D., Bygrave, A., Ploemacher, R., and Grosveld, F. 1995. Defective hae-matopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature 375:316–318.PubMedGoogle Scholar
  78. Olweus, J., Terstappen, L. W., Thompson, P. A., and Lund-Johansen, F. 1996. Expression and function of receptors for stem cell factor and erythropoietin during lineage commitment of human hematopoietic progenitor cells. Blood 88:1594–1607.PubMedGoogle Scholar
  79. Paffett-Lugassy, N., Hsia, N., Fraenke, P. G., Paw, B., Leshinsky, I., Barut, B., Bahary, N., Caro, J., Handin, R., and Zon, L. I. 2007. Functional conservation of erythropoietin signaling in zebrafish. Blood 110:2718–2726PubMedGoogle Scholar
  80. Palis, J., Robertson, S., Kennedy, M., Wall, C. and Keller, G. 1999. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126, 5073–5084.PubMedGoogle Scholar
  81. Pasini, E. M., Kirkegaard, M., Mortensen, P., Lutz, H. U., Thomas, A. W., and Mann, M. 2006. In-depth analysis of the membrane and cytosolic proteome of red blood cells. Blood 108:791–801.PubMedGoogle Scholar
  82. Perkins, A. C., Sharpe, A. H., and Orkin, S. H. 1995. Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature 375:318–322.PubMedGoogle Scholar
  83. Peschle, C., Mavilio, F, Care, A., Migliaccio, G., Migliaccio, A. R., Salvo, G., Samoggia, P., Petti, S., Guerriero, R., Marinucci, M., Lazzaro, D., Russo, G., and Mastroberardino, G. 1985. Haemoglobin switching in human embryos: Asynchrony of the ζ — > α and ε — > γ-globin switches in primitive and definitive erythropoietic lineage. Nature 313:235–238.PubMedGoogle Scholar
  84. Pevny, L., Simon, M. C., Robertson, E., Klein, W. H., Tsai, S. F., D'Agati, V., Orkin, S. H., and Costantini, F. 1991. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 349:257–260.PubMedGoogle Scholar
  85. Pilon, A. M., Nilson, D. G., Zhou, D., Sangerman, J., Townes, T. M., Bodine, D. M., and Gallagher, P. G. 2006. Alterations in expression and chromatin configuration of the alpha hemoglobin-stabilizing protein gene in erythroid Kruppel-like factor-deficient mice. Mol Cell Biol 26:4368–4377.PubMedGoogle Scholar
  86. Porcher, C., Swat, W., Rockwell, K., Fujiwara, Y., Alt, F. W., and Orkin, S. H. 1996. The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 86:47–57.PubMedGoogle Scholar
  87. Raich, N., Enver, T., Nakamoto, B., Josephson, B., Papayannopoulou, T., and Stamatoyannopoulos, G. 1990. Autonomous developmental control of human embryonic globin gene switching in transgenic mice. Science 250:1147–1149.PubMedGoogle Scholar
  88. Remy, I., Wilson, I. A., and Michnick, S. W. 1999. Erythropoietin receptor activation by a ligand-induced conformation change. Science 283:990–993.PubMedGoogle Scholar
  89. Rhodes, M. M., Kopsombut, P., Bondurant, M. C., Price, J. O., and Koury, M. J. 2008. Adherence to macrophages in erythroblastic islands enhances erythroblast proliferation and increases erythrocyte production by a different mechanism than erythropoietin. Blood 111:1700–1708.PubMedGoogle Scholar
  90. Rich, I. N. 1986. A role for the macrophage in normal hematopoiesis. Exp Hematol 14:746–751.PubMedGoogle Scholar
  91. Rich, I. N. and Kubanek, B. 1976. Erythroid colony formation in foetal liver and adult bone marrow and spleen from the mouse. Blood 33:171–180.Google Scholar
  92. Rich, I. N. and Kubanek, B. 1979. The ontogeny of erythropoiesis in the mouse detected by the erythroid colony-forming technique. J Embryol Exp Morphol 50:57–74.PubMedGoogle Scholar
  93. Robb, L., Lyons, I., Li, R., Hartley, L., Köntgen, F., Harvey, R. P., Metcalf, D., Begley, C. G. 1995. Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. Proc Natl Acad Sci USA 92:7075–7079.PubMedGoogle Scholar
  94. Robb, L., Elwood, N. J., Elefanty, A. G., Kontgen, F., Li, R., Barnett, L. D., and Begley, C. G. 1996. The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse. EMBO J 15:4123–4129.PubMedGoogle Scholar
  95. Rodriguez, P., Bonte, E., Krijgsveld, J., Kolodziej, K. E., Guyot, B., Heck, A. J., Vyas, P., de Boer, E., Grosveld, F., and Strouboulis, J. 2005. GATA-1 forms distinct activating and repressive complexes in erythroid cells. EMBO J 24:2354–2366.PubMedGoogle Scholar
  96. Sadahira, Y., Yoshino, T., and Monobe, Y. 1995. Very late activation antigen 4-vascular cell adhesion molecule 1 interaction is involved in the formation of erythroblast islands. J Exp Med 181:411–415.PubMedGoogle Scholar
  97. Sangiorgi, F., Woods, C. M. and Lazarides, E. 1990. Vimentin downregulation is an inherent feature of murine erythropoiesis and occurs independently of lineage. Development 110:85–96.PubMedGoogle Scholar
  98. Sasaki, K., and Matsamura, G. 1986. Haemopoietic cells of yolk sac and liver in the mouse embryo: A light and electron microscopical study. J Anat 148:87–97.PubMedGoogle Scholar
  99. Sathyanarayana, P., Menon, M. P., Bogacheva, O., Bogachev, O., Niss, K., Kapelle, W. S., Houde, E., Fang, J., and Wojchowski, D. M. 2007. Erythropoietin modulation of podocalyxin and a proposed erythroblast niche. Blood 110:509–518.PubMedGoogle Scholar
  100. Schuh, A. H., Tipping, A. J., Clark, A. J., Hamlett, I., Guyot, B., Iborra, F. J., Rodriguez, P., Strouboulis, J., Enver, T., Vyas, P., and Porcher, C. 2005. ETO-2 associates with SCL in eryth-roid cells and megakaryocytes and provides repressor functions in erythropoiesis. Mol Cell Biol 25:10235–10250.PubMedGoogle Scholar
  101. Schweers, R. L., Zhang, J., Randall, M. S., Loyd, M. R., Li, W., Dorsey, F. C., Kundu, M., Opferman, J. T., Cleveland, J. L., Miller, J. L., and Ney, P. A. 2007. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 104:19500–19505.PubMedGoogle Scholar
  102. Semenza, G. L. and Wang, G. L. 1992. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12:5447–5454.PubMedGoogle Scholar
  103. Shimizu, R., Takahashi, S., Ohneda, K., Engel, J. D. and Yamamoto, M. 2001. In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis. EMBO J 20:5250–5260.PubMedGoogle Scholar
  104. Shivdasani, R. A., Mayer, E. L., and Orkin, S. H. 1995. Absence of blood formation in mice lacking T-cell leukemia oncoprotein tal-1/SCL. Nature 373:432–434.PubMedGoogle Scholar
  105. Silva, M., Benito, A., Sanz, C., Prosper, F., Ekhterae, D., Nuñez, G., and Fernandez-Luna, J. L. 1999. Erythropoietin can induce the expression of bcl-x(L. through Stat5 in erythropoietin-dependent progenitor cell lines. J Biol Chem 274:22165–9.PubMedGoogle Scholar
  106. Silver, L, and Palis, J. 1997. Initiation of murine embryonic erythropoiesis: A spatial analysis. Blood 89:1154–1164.PubMedGoogle Scholar
  107. Simpson, C. F. and Kling, J. M. 1967. The mechanism of denucleation in circulating erythroblasts. J Cell Biol 35:237–245.PubMedGoogle Scholar
  108. Sivertsen, E. A., Hystad, M. E., Gutzkow, K. B., Dosen, G., Smeland, E. B., Blomhoff, H. K., and Myklebust, J. H. 2006. PI3K/Akt-dependent Epo-induced signalling and target genes in human early erythroid progenitor cells. Br J Haematol 135:117–128.PubMedGoogle Scholar
  109. Skutelsky, E., and Danon, D. 1970. Comparative study of nuclear expulsion from the late eryth-roblast and cytokinesis. Exp Cell Res 60:427–436.PubMedGoogle Scholar
  110. Socolovsky, M., Fallon, A. E., Wang, S., Brugnara, C., and Lodish, H. F. 1999. Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: A direct role for Stat5 in Bcl-X(L. induction. Cell 98:181–191.PubMedGoogle Scholar
  111. Soni, S., Bala, S., Gwynn, B., Sahr, K. E., Peters, L. L., and Hanspal, M. 2006. Absence of eryth-roblast macrophage protein Emp. leads to failure of erythroblast nuclear extrusion. J Biol Chem 281:20181–20189.PubMedGoogle Scholar
  112. Southwood, C. M., Downs, K. M., and Bieker, J. J. 1996. Erythroid Krüppel-like factor exhibits an early and sequentially localized pattern of expression during mammalian erythroid ontogeny. Dev Dyn 206:248–259.PubMedGoogle Scholar
  113. Spring, F. A., Parsons, S. F., Ortlepp, S., Olsson, M. L., Sessions, R., Brady, R. L., and Anstee D. J. 2001. Intercellular adhesion molecule-4 binds alpha(4)beta(1. and alpha(V)-family integrins through novel integrin-binding mechanisms. Blood 98:458–466.PubMedGoogle Scholar
  114. Stamatoyannopoulos, G. 2005. Control of globin gene expression during development and eryth-roid differentiation. Exp Hematol 33:259–271.PubMedGoogle Scholar
  115. Steiner, R., and Vogel, H. 1973. On the kinetics of erythroid cell differentiation in fetal mice: I. Microspectrophotometric determination of the hemoglobin content in erythroid cells during gestation. J Cell Physiol 81:323–338.Google Scholar
  116. Stephenson, J. R., Axelrad, A., McLeod, D., and Shreeve, M. 1971. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci USA 68:1542–1546.PubMedGoogle Scholar
  117. Swiers, G., Patient, R., and Loose, M. 2006. Genetic regulatory networks programming hemat-opoietic stem cells and erythroid lineage specification. Dev Biol 294:525–540.PubMedGoogle Scholar
  118. Tanabe, O., McPhee, D., Kobayashi, S., Shen, Y., Brandt, W., Jiang, X., Campbell, A. D., Chen, Y. T., Chang, C., Yamamoto, M., Tanimoto, K., and Engel, J. D. 2007. Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors, TR2 and TR4 . EMBO J 26:2295–2306.PubMedGoogle Scholar
  119. Tavassoli, M. 1991. Embryonic and fetal hemopoiesis: An overview. Blood Cells 1:269–281.Google Scholar
  120. Tinsley, J. C., Jr., Moore, C. V., Dubach, R., Minnich, V., and Grinstein, M. 1949. The role of oxygen in the regulation of erythropoiesis; depression of the rate of delivery of new red cells to the blood by high concentrations of inspired oxygen. J Clin Invest 28:1544–1564.PubMedGoogle Scholar
  121. Trimborn, T., Bribnau, J., Grosveld, F., and Fraser, P. 1999. Mechanisms of developmental control of transcription in the murine α- and β-globin loci. Genes Dev 13:112–124.PubMedGoogle Scholar
  122. Tsang, A. P., Visvader, J. E., Turner, C. A., Fujiwara, Y., Yu, C., Weiss, M. J., Crossley, M., and Orkin, S. H. 1997. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell 90:109–119.PubMedGoogle Scholar
  123. Tsang, A. P., Fujiwara, Y., Hom, D. B. and Orkin, S. H. 1998. Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG . Genes Dev 15:1176–1188.Google Scholar
  124. Uddin, S., Kottegoda, S., Stigger, D., Platanias, L. C., and Wickrema, A. 2000. Activation of the Akt/FKHRL1 pathway mediates the antiapoptotic effects of erythropoietin in primary human erythroid progenitors. Biochem Biophys Res Commun 275:16–19.PubMedGoogle Scholar
  125. Wadman, I. A., Osada, H., Grütz, G. G., Agulnick, A. D., Westphal, H., Forster, A., and Rabbitts, T. H. 1997 . 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 16:3145–3157.PubMedGoogle Scholar
  126. Warren, A. J., Colledge, W. H., Carlton, M. B. L., Evans, M., Smith, A. J. H., and Rabbitts, T. H. 1994. T he oncogenic cysteine-rich LIM domain protein is essential for erythroid development. Cell 78:45–57.PubMedGoogle Scholar
  127. Wong, P. M. C., Chung, S. W., Chui, D. H. K., and Eaves, C. J. 1986. Properties of the earliest clonogenic hematopoietic precursors to appear in the developing murine yolk sac . Proc Natl Acad Sci USA 83:3851–3854.PubMedGoogle Scholar
  128. Wu, H., Liu, X., Jaenisch, R., and Lodish, H. F. 1995. Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor . Cell 83:59–67.PubMedGoogle Scholar
  129. Wu, H., Klingmüller, U., Acurio, A., Hsiao, J. G., and Lodish, H. F. 1997. Functional interaction of erythropoietin and stem cell factor receptors is essential for erythroid colony formation . Proc Natl Acad Sci USA 94:1806–1810.PubMedGoogle Scholar
  130. Yamada, Y., Warren, A. J., Dobson, C., Forster, A., Pannell, R., and Rabbitts, T. H. 1998. The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis . Proc Natl Acad Sci USA 95:3890–3895.PubMedGoogle Scholar
  131. Yoshida, H., Kawane, K., Koike, M., Mori, Y., Uchiyama, Y. and Nagata, S. 2005. Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature 437:754–758.PubMedGoogle Scholar
  132. Zhan, M., Miller, C., and Papayannopoulou, T., Stamatoyannopoulos, G., and Song, C.-Z. 2007. MicroRNA expression dynamics during murine and human erythroid differentiation. Exp Hematol 35:1015–1025.PubMedGoogle Scholar
  133. Zhang, Y., Payne, K. J., Zhu, Y., Price, M. A., Parrish, Y. K., Zielinska, E., Barsky, L. W., and Crooks, G. M. 2005. SCL expression at critical points in human hematopoietic lineage commitment. Stem Cells 23:852–860.PubMedGoogle Scholar
  134. Zheng, J., Kitajima, K., Sakai, E., Kimura, T., Minegishi, N., Yamamoto, M., and Nakano, T. 2006. Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells. Blood 107:520–527.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Pediatrics, Center for Pediatric Biomedical ResearchUniversity of Rochester Medical CenterRochesterUSA

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