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EMBRYONIC STEM CELLS

Sequential Analysis of - and ß-Globin Gene Expression During Erythropoietic Differentiation from Primate Embryonic Stem Cells

^aDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
^bLaboratory of Embryonic Stem Cell Research, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan;
^cDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA;
^dResearch Center for Animal Life Science, Shiga University of Medical Science, Ohtsu, Japan;
^eDivision of Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan;
^fDepartment of Development and Differentiation, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan

Key Words. Embryonic stem cells • Erythroid progenitors

Correspondence: Tatsutoshi Nakahata, M.D., Ph.D., Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 Japan. Telephone: 81-75-751-3290; Fax: 81-75-752-2361; e-mail: tnakaha{at}kuhp.kyoto-u.ac.jp

Received on April 7, 2006; accepted for publication on July 26, 2006.

First published online in STEM CELLS EXPRESS  August 3, 2006.


The temporal pattern of embryonic, fetal, and adult globin expression in the ( ) and ß ( and ß) clusters were quantitatively analyzed at the transcriptional and translational levels in erythrocytes induced from primate embryonic stem cells in vitro. When vascular endothelial growth factor receptor-2^high CD34⁺ cells were harvested and reseeded onto OP9 stromal cells, two-wave erythropoiesis occurred sequentially. Immunostaining and real-time reverse transcription-polymerase chain reaction analyses of floating mature erythrocytes revealed that globin switches occurred in parallel with the erythropoietic transition. Colony-forming assays showed replacement of primitive clonogenic progenitor cells with definitive cells during culturing. A decline in embryonic - and -globin expression at the translational level occurred in individual definitive erythroid progenitors. Expression of ß-globin in individual definitive erythroid progenitors was upregulated in the presence of OP9 stromal cells. Thus, this system reproduces early hematopoietic development in vitro and can serve as a model for analyzing the mechanisms of the globin switch in humans.

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				F. Ma, Y. Ebihara, K. Umeda, H. Sakai, S. Hanada, H. Zhang, Y. Zaike, E. Tsuchida, T. Nakahata, H. Nakauchi, et al. Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis PNAS, September 2, 2008; 105(35): 13087 - 13092. [Abstract] [Full Text] [PDF]