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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2400-2408. Prepublished online as a Blood First Edition Paper on November 16, 2007; DOI 10.1182/blood-2007-07-102087. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-102087v1 111/4/2400    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Qiu, C. Articles by Bouhassira, E. E. Search for Related Content PubMed PubMed Citation Articles by Qiu, C. Articles by Bouhassira, E. E. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Globin switches in yolk sac–like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells Caihong Qiu1, Emmanuel N. Olivier1, Michelle Velho1, and Eric E. Bouhassira1 1 Einstein Center for Human Embryonic Stem Cell Research, Department of Medicine, Hematology and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY We have previously shown that coculture of human embryonic stem cells (hESCs) for 14 days with immortalized fetal hepatocytes yields CD34+ cells that can be expanded in serum-free liquid culture into large numbers of megaloblastic nucleated erythroblasts resembling yolk sac–derived cells. We show here that these primitive erythroblasts undergo a switch in hemoglobin (Hb) composition during late terminal erythroid maturation with the basophilic erythroblasts expressing predominantly Hb Gower I (22) and the orthochromatic erythroblasts hemoglobin Gower II (22). This suggests that the switch from Hb Gower I to Hb Gower II, the first hemoglobin switch in humans is a maturation switch not a lineage switch. We also show that extending the coculture of the hESCs with immortalized fetal hepatocytes to 35 days yields CD34+ cells that differentiate into more developmentally mature, fetal liver–like erythroblasts, that are smaller, express mostly fetal hemoglobin, and can enucleate. We conclude that hESC-derived erythropoiesis closely mimics early human development because the first 2 human hemoglobin switches are recapitulated, and because yolk sac–like and fetal liver–like cells are sequentially produced. Development of a method that yields erythroid cells with an adult phenotype remains necessary, because the most mature cells that can be produced with current systems express less than 2% adult β-globin mRNA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Klimchenko, M. Mori, A. DiStefano, T. Langlois, F. Larbret, Y. Lecluse, O. Feraud, W. Vainchenker, F. Norol, and N. Debili A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis Blood, August 20, 2009; 114(8): 1506 - 1517. [Abstract] [Full Text] [PDF] P. S. Woll, B. Grzywacz, X. Tian, R. K. Marcus, D. A. Knorr, M. R. Verneris, and D. S. Kaufman Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity Blood, June 11, 2009; 113(24): 6094 - 6101. [Abstract] [Full Text] [PDF] E. E. Bouhassira Toward the manufacture of red blood cells? Blood, December 1, 2008; 112(12): 4362 - 4363. [Full Text] [PDF] S.-J. Lu, Q. Feng, J. S. Park, L. Vida, B.-S. Lee, M. Strausbauch, P. J. Wettstein, G. R. Honig, and R. Lanza Biologic properties and enucleation of red blood cells from human embryonic stem cells Blood, December 1, 2008; 112(12): 4475 - 4484. [Abstract] [Full Text] [PDF]

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