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Blood, 1 August 2005, Vol. 106, No. 3, pp. 860-870. Prepublished online as a Blood First Edition Paper on April 14, 2005; DOI 10.1182/blood-2004-11-4522. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-11-4522v1 106/3/860    most recent Alert me when this article is cited Alert me if a correction is posted 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 Civin, C. I Search for Related Content PubMed PubMed Citation Articles by Zambidis, E. T Articles by Civin, C. I Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 30, 2004 Accepted April 3, 2005 Hematopoietic differentiation of human embryonic stem cells progresses through sequential hemato-endothelial, primitive, and definitive stages resembling human yolk sac development Elias T Zambidis*, Bruno Peault, Tea Soon Park, Fred Bunz, and Curt I Civin Divisions of Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, Baltimore, MD, USA Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Radiation Biology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, Baltimore, MD, USA Divisions of Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, Baltimore, MD, USA * Corresponding author; email: ezambid1{at}jhmi.edu. We elucidate the cellular and molecular kinetics of the step-wise differentiation of human embryonic stem cells (hESC) to primitive and definitive erythro-myelopoiesis from human embryoid bodies (hEB) in serum-free clonogenic assays. Hematopoiesis initiates from CD45- hEB cells with emergence of semi-adherent mesodermal-hemato-endothelial (MHE) colonies that can generate endothelium, and form organized, yolk-sac-like structures that secondarily generate multipotent primitive hematopoietic stem-progenitor cells (HSPC), erythroblasts, and CD13+CD45+ macrophages. A first wave of hematopoiesis follows MHE colony emergence, and is predominated by primitive erythropoiesis characterized by a brilliant red hemoglobinization, CD71/CD325a (glycophorin A) expression, and exclusively embryonic/fetal hemoglobin expression. A second wave of definitive-type BFU-e, CFU-e, GM-CFC, and multi-lineage colony-forming cells (CFC) follows next from hEB progenitors. These stages of hematopoiesis proceed spontaneously from hEB-derived cells without requirement for supplemental growth factors during hEB differentiation. Gene-expression analysis of differentiating hEB revealed that initiation of hematopoiesis correlated with increased levels of SCL/TAL1, GATA1, GATA2, CD34, CD31, and the homeobox gene-regulating factor CDX4. These data indicate that hematopoietic differentiation of hESC models the earliest events of embryonic and definitive hematopoiesis in a manner resembling human yolk sac development, thus providing a valuable tool for dissecting the earliest events in human HSPC genesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-J. Lu, Q. Feng, J. S. Park, L. Vida, B.-S. Lee, M. Strausbauch, P. J. Wettstein, G. R. Honig, and R. 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