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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3601-3614. Prepublished online as a Blood First Edition Paper on September 5, 2008; DOI 10.1182/blood-2008-03-144766. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-03-144766v1 blood-2008-03-144766v2 112/9/3601    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 Zambidis, E. T. Articles by Péault, B. Search for Related Content PubMed PubMed Citation Articles by Zambidis, E. T. Articles by Péault, B. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells Elias T. Zambidis1,2, Tea Soon Park3, Wayne Yu2, Ada Tam1, Michal Levine1, Xuan Yuan1,2, Marina Pryzhkova1, and Bruno Péault3 1 Institute of Cell Engineering, Stem Cell Program, Johns Hopkins University School of Medicine, and 2 Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; and 3 Stem Cell Research Center, Department of Pediatrics, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, PA We report that angiotensin-converting enzyme (ACE), a critical physiologic regulator of blood pressure, angiogenesis, and inflammation, is a novel marker for identifying hemangioblasts differentiating from human embryonic stem cells (hESC). We demonstrate that ACE+CD45–CD34+/– hemangioblasts are common yolk sac (YS)–like progenitors for not only endothelium but also both primitive and definitive human lymphohematopoietic cells. Thrombopoietin and basic fibroblast growth factor are identified as critical factors for the proliferation of human hemangioblasts. The developmental sequence of human embryoid body hematopoiesis is remarkably congruent to the timeline of normal human YS development, which occurs during weeks 2 to 6 of human gestation. Furthermore, ACE and the renin-angiotensin system (RAS) directly regulate hemangioblast expansion and differentiation via signaling through the angiotensin II receptors AGTR1 and AGTR2. ACE enzymatic activity is required for hemangioblast expansion, and differentiation toward either endothelium or multipotent hematopoietic progenitors is dramatically augmented after manipulation of angiotensin II signaling with either AGTR1- or AGTR2-specific inhibitors. The RAS can therefore be exploited to direct the hematopoietic or endothelial fate of hESC-derived hemangioblasts, thus providing novel opportunities for human tissue engineering. Moreover, the initial events of human hematoendotheliogenesis can be delineated in a manner previously impossible because of inaccessibility to early human embryonic tissues. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. S. Kaufman Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells Blood, October 22, 2009; 114(17): 3513 - 3523. [Abstract] [Full Text] [PDF] C. Graziano, S. Carone, E. Panza, F. Marino, P. Magini, G. Romeo, A. Pession, and M. Seri Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation Blood, August 20, 2009; 114(8): 1655 - 1657. [Abstract] [Full Text] [PDF] T. S. Park and E. T. Zambidis A role for the renin-angiotensin system in hematopoiesis Haematologica, June 1, 2009; 94(6): 745 - 747. [Full Text] [PDF] S. Heringer-Walther, K. Eckert, S.-M. Schumacher, L. Uharek, A. Wulf-Goldenberg, F. Gembardt, I. Fichtner, H.-P. Schultheiss, K. Rodgers, and T. Walther Angiotensin-(1-7) stimulates hematopoietic progenitor cells in vitro and in vivo Haematologica, June 1, 2009; 94(6): 857 - 860. [Abstract] [Full Text] [PDF]

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