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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2406-2415.
Prepublished online as a Blood First Edition Paper on November 7, 2006; DOI 10.1182/blood-2006-06-031039.


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Submitted June 26, 2006
Accepted October 25, 2006

{alpha}4-integrin+ endothelium derived from primate embryonic stem cells generates both primitive and definitive hematopoietic cells

Gen Shinoda, Katsutsugu Umeda, Toshio Heike, Masato Arai, Akira Niwa, Feng Ma, Hirofumi Suemori, Hong Yuan Luo, David H. K. Chui, Ryuzo Torii, Masabumi Shibuya, Norio Nakatsuji, and Tatsutoshi Nakahata*

Graduate School of Medicine, Kyoto University, Japan
Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Japan
Boston Universal School of Medicine, Boston, MA, United States
Shiga University of Medical Science, Japan
Institute of Medical Science, University of Tokyo, Japan
Institute for Frontier Medical Sciences, Kyoto Univer, Japan

* Corresponding author; email: tnakaha{at}kuhp.kyoto-u.ac.jp.

The mechanism of commencement of hematopoiesis in blood islands of the yolk sac and the aorta-gonad-mesonephros (AGM) region during primate embryogenesis remains elusive. In this study, we demonstrate that VE-cadherin+CD45- endothelial cells derived from nonhuman primate embryonic stem cells are able to generate primitive and definitive hematopoietic cells sequentially, as revealed by immunostaining of floating erythrocytes and colony-forming assay in cultures. Single bipotential progenitors for hematopoietic and endothelial lineages are included in this endothelial cell population. Furthermore, hemogenic activity of these endothelial cells is observed exclusively in the {alpha}4-integrin+ subpopulation and bipotential progenitors are 4-fold enriched in this subpopulation. The kinetics of this hemogenic subpopulation is similar to that of hemogenic endothelial cells previously reported in the yolk sac and the AGM region in vivo, in that they emerge only for a limited time. We suggest that VE-cadherin+CD45-{alpha}4-integrin+ endothelial cells are involved in primitive as well as definitive hematopoiesis during primate embryogenesis, although VE-cadherin-CD45-{alpha}4-integrin+ cells are primary sources for primitive hematopoiesis.


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