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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2095-2105. Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-02-003327. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2006-02-003327v1 108/6/2095    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 Vodyanik, M. A. Articles by Slukvin, I. I. Search for Related Content PubMed PubMed Citation Articles by Vodyanik, M. A. Articles by Slukvin, I. I. Related Collections Hematopoiesis and Stem Cells Stem Cells in Hematology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures Maxim A. Vodyanik, James A. Thomson, and Igor I. Slukvin From the National Primate Research Center, University of Wisconsin Graduate School, Madison; WiCell Research Institute, Madison, WI; Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison; Department of Anatomy, University of Wisconsin Medical School, Madison; and the Genome Center of Wisconsin, University of Wisconsin, Madison. During hematopoietic differentiation of human embryonic stem cells (hESCs), early hematopoietic progenitors arise along with endothelial cells within the CD34+ population. Although hESC-derived hematopoietic progenitors have been previously identified by functional assays, their phenotype has not been defined. Here, using hESC differentiation in coculture with OP9 stromal cells, we demonstrate that early progenitors committed to hematopoietic development could be identified by surface expression of leukosialin (CD43). CD43 was detected on all types of emerging clonogenic progenitors before expression of CD45, persisted on differentiating hematopoietic cells, and reliably separated the hematopoietic CD34+ population from CD34+CD43–CD31+KDR+ endothelial and CD34+CD43–CD31–KDR– mesenchymal cells. Furthermore, we demonstrated that the first-appearing CD34+CD43+CD235a+CD41a+/–CD45– cells represent precommitted erythro-megakaryocytic progenitors. Multipotent lymphohematopoietic progenitors were generated later as CD34+CD43+CD41a–CD235a–CD45– cells. These cells were negative for lineage-specific markers (Lin–), expressed KDR, VE-cadherin, and CD105 endothelial proteins, and expressed GATA-2, GATA-3, RUNX1, C-MYB transcription factors that typify initial stages of definitive hematopoiesis originating from endothelial-like precursors. Acquisition of CD45 expression by CD34+CD43+CD45–Lin– cells was associated with progressive myeloid commitment and a decrease of B-lymphoid potential. CD34+CD43+CD45+Lin– cells were largely devoid of VE-cadherin and KDR expression and had a distinct FLT3highGATA3lowRUNX1lowPU1highMPOhighIL7RAhigh gene expression profile. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: 34 + 43 = early human blood lineage Eric E. Bouhassira Blood 2006 108: 1787-1788. [Full Text] [PDF] This article has been cited by other articles: F. Timmermans, I. Velghe, L. Vanwalleghem, M. De Smedt, S. Van Coppernolle, T. Taghon, H. D. Moore, G. Leclercq, A. W. Langerak, T. Kerre, et al. Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones J. Immunol., June 1, 2009; 182(11): 6879 - 6888. [Abstract] [Full Text] [PDF] K.-D. Choi, J. Yu, K. Smuga-Otto, G. Salvagiotto, W. Rehrauer, M. Vodyanik, J. Thomson, and I. Slukvin Hematopoietic and Endothelial Differentiation of Human Induced Pluripotent Stem Cells Stem Cells, March 1, 2009; 27(3): 559 - 567. [Abstract] [Full Text] [PDF] C. Qiu, E. N. Olivier, M. Velho, and E. E. Bouhassira Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells Blood, February 15, 2008; 111(4): 2400 - 2408. [Abstract] [Full Text] [PDF] R. P. Davis, E. S. Ng, M. Costa, A. K. Mossman, K. Sourris, A. G. Elefanty, and E. G. Stanley Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors Blood, February 15, 2008; 111(4): 1876 - 1884. [Abstract] [Full Text] [PDF] P. S. Woll, J. K. Morris, M. S. Painschab, R. K. Marcus, A. D. Kohn, T. L. Biechele, R. T. Moon, and D. S. Kaufman Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells Blood, January 1, 2008; 111(1): 122 - 131. [Abstract] [Full Text] [PDF] E. C. Torchia, K. Boyd, J. E. Rehg, C. Qu, and S. J. Baker EWS/FLI-1 Induces Rapid Onset of Myeloid/Erythroid Leukemia in Mice Mol. Cell. Biol., November 15, 2007; 27(22): 7918 - 7934. [Abstract] [Full Text] [PDF] L. S. Ferreira, S. Gerecht, H. F. Shieh, N. Watson, M. A. Rupnick, S. M. Dallabrida, G. Vunjak-Novakovic, and R. Langer Vascular Progenitor Cells Isolated From Human Embryonic Stem Cells Give Rise to Endothelial and Smooth Muscle Like Cells and Form Vascular Networks In Vivo Circ. Res., August 3, 2007; 101(3): 286 - 294. [Abstract] [Full Text] [PDF] F. Timmermans, F. Van Hauwermeiren, M. De Smedt, R. Raedt, F. Plasschaert, M. L. De Buyzere, T. C. Gillebert, J. Plum, and B. Vandekerckhove Endothelial Outgrowth Cells Are Not Derived From CD133+ Cells or CD45+ Hematopoietic Precursors Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1572 - 1579. [Abstract] [Full Text] [PDF]

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