SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-06-1699. This Article Full Text (PDF) All Versions of this Article: 2002-06-1699v1 101/2/508    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 Mikkola, H. K Articles by Orkin, S. H Search for Related Content PubMed PubMed Citation Articles by Mikkola, H. K Articles by Orkin, S. H Social Bookmarking                   What's this? Submitted June 10, 2002 Accepted August 14, 2002 Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo Hanna K Mikkola, Yuko . Fujiwara, Thorsten M Schlaeger, David Traver, and Stuart H Orkin* Division of Hematology/Oncology, Children's Hospital, HHMI, Boston, MA, USA; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA Howard Hughes Medical Institute, Boston, MA, USA Division of Hematology/Oncology, Children's Hospital, HHMI, Boston, MA, USA * Corresponding author; email: orkin{at}rascal.med.harvard.edu. Murine hematopoietic cells originate from mesoderm in a process that requires the transcription factor SCL/Tal1. To define steps in the commitment to blood cell fate we compared wild type and SCL-/- embryonic stem cell differentiation in vitro and identified CD41 (GpIIb) as the earliest surface marker lacking from SCL-/- embryoid bodies (EBs). Culture of FACS sorted cells from EBs showed that definitive hematopoietic progenitors were highly enriched in the CD41+ fraction, whereas endothelial cells developed from CD41- cells. In the mouse embryo, expression of CD41 was detected in yolk sac blood islands and in fetal liver. In yolk sac and EBs, the pan-hematopoietic marker CD45 appeared in a subpopulation of CD41+ cells. However, multilineage hematopoietic colonies developed not only from CD45+CD41+ cells but also from CD45-CD41+ cells, suggesting that CD41 rather than CD45 marks definitive CFU-C at the embryo stage. In contrast, fetal liver CFU-C were CD45+ and only a subfraction expressed CD41, demonstrating downregulation of CD41 by the fetal liver stage. In yolk sac and EBs, CD41 was coexpressed with embryonic HSC markers c-kit and CD34. Sorting for CD41 and c-kit expression enriched for definitive hematopoietic progenitors. Furthermore, the CD41+c-kit+ population was missing from runx1/AML1-/- EBs that lack definitive hematopoiesis. These results suggest that expression of CD41, a candidate target gene of SCL/Tal1, and c-kit define the divergence of definitive hematopoiesis from endothelial cells during development. Although CD41 is commonly referred to as megakaryocyte/platelet integrin in adult hematopoiesis, these results implicate a wider role for CD41 during murine ontogeny. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Gandillet, A. G. Serrano, S. Pearson, M. Lie-A-Ling, G. Lacaud, and V. Kouskoff Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification Blood, November 26, 2009; 114(23): 4813 - 4822. [Abstract] [Full Text] [PDF] D. J. Stumpo, H. E. Broxmeyer, T. Ward, S. Cooper, G. Hangoc, Y. J. Chung, W. C. Shelley, E. K. Richfield, M. K. Ray, M. C. Yoder, et al. Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis Blood, September 17, 2009; 114(12): 2401 - 2410. [Abstract] [Full Text] [PDF] O. Klimchenko, M. Mori, A. DiStefano, T. Langlois, F. Larbret, Y. Lecluse, O. Feraud, W. Vainchenker, F. Norol, and N. Debili A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis Blood, August 20, 2009; 114(8): 1506 - 1517. [Abstract] [Full Text] [PDF] S. T. Chou, E. Khandros, L. C. Bailey, K. E. Nichols, C. R. Vakoc, Y. Yao, Z. Huang, J. D. Crispino, R. C. Hardison, G. A. Blobel, et al. Graded repression of PU.1/Sfpi1 gene transcription by GATA factors regulates hematopoietic cell fate Blood, July 30, 2009; 114(5): 983 - 994. [Abstract] [Full Text] [PDF] S. L. McKinney-Freeman, O. Naveiras, F. Yates, S. Loewer, M. Philitas, M. Curran, P. J. Park, and G. Q. Daley Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells Blood, July 9, 2009; 114(2): 268 - 278. [Abstract] [Full Text] [PDF] T. Yamane, N. Hosen, H. Yamazaki, and I. L. Weissman Expression of AA4.1 marks lymphohematopoietic progenitors in early mouse development PNAS, June 2, 2009; 106(22): 8953 - 8958. [Abstract] [Full Text] [PDF] C. Gekas, K. E. Rhodes, L. M. Gereige, H. Helgadottir, R. Ferrari, S. K. Kurdistani, E. Montecino-Rodriguez, R. Bassel-Duby, E. Olson, A. V. Krivtsov, et al. Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis Blood, April 9, 2009; 113(15): 3461 - 3471. [Abstract] [Full Text] [PDF] S. Irion, M.C. Nostro, S.J. Kattman, and G.M. Keller Directed Differentiation of Pluripotent Stem Cells: From Developmental Biology to Therapeutic Applications Cold Spring Harb Symp Quant Biol, March 27, 2009; (2009) sqb.2008.73.065v1. [Abstract] [PDF] T. Yokota, K. Oritani, S. Butz, K. Kokame, P. W. Kincade, T. Miyata, D. Vestweber, and Y. Kanakura The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice Blood, March 26, 2009; 113(13): 2914 - 2923. [Abstract] [Full Text] [PDF] H.-T. Huang and L.I. Zon Regulation of Stem Cells in the Zebra Fish Hematopoietic System Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.029v1. [Abstract] [PDF] B. S. Coller and S. J. Shattil The GPIIb/IIIa (integrin {alpha}IIb{beta}3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend Blood, October 15, 2008; 112(8): 3011 - 3025. [Abstract] [Full Text] [PDF] L. C. Goldie, J. L. Lucitti, M. E. Dickinson, and K. K. Hirschi Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis Blood, October 15, 2008; 112(8): 3194 - 3204. [Abstract] [Full Text] [PDF] B. Valamehr, S. J. Jonas, J. Polleux, R. Qiao, S. Guo, E. H. Gschweng, B. Stiles, K. Kam, T.-J. M. Luo, O. N. Witte, et al. Hydrophobic surfaces for enhanced differentiation of embryonic stem cell-derived embryoid bodies PNAS, September 23, 2008; 105(38): 14459 - 14464. [Abstract] [Full Text] [PDF] M.-J. Yoon, B.-K. Koo, R. Song, H.-W. Jeong, J. Shin, Y.-W. Kim, Y.-Y. Kong, and P.-G. Suh Mind bomb-1 Is Essential for Intraembryonic Hematopoiesis in the Aortic Endothelium and the Subaortic Patches Mol. Cell. Biol., August 1, 2008; 28(15): 4794 - 4804. [Abstract] [Full Text] [PDF] J. Y. Bertrand, A. D. Kim, S. Teng, and D. Traver CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis Development, May 15, 2008; 135(10): 1853 - 1862. [Abstract] [Full Text] [PDF] S. L. McKinney-Freeman, C. Lengerke, I.-H. Jang, S. Schmitt, Y. Wang, M. Philitas, J. Shea, and G. Q. Daley Modulation of murine embryonic stem cell-derived CD41+c-kit+ hematopoietic progenitors by ectopic expression of Cdx genes Blood, May 15, 2008; 111(10): 4944 - 4953. [Abstract] [Full Text] [PDF] S. Pearson, P. Sroczynska, G. Lacaud, and V. Kouskoff The stepwise specification of embryonic stem cells to hematopoietic fate is driven by sequential exposure to Bmp4, activin A, bFGF and VEGF Development, April 15, 2008; 135(8): 1525 - 1535. [Abstract] [Full Text] [PDF] X. Zhao, V. Jankovic, A. Gural, G. Huang, A. Pardanani, S. Menendez, J. Zhang, R. Dunne, A. Xiao, H. Erdjument-Bromage, et al. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity Genes & Dev., March 1, 2008; 22(5): 640 - 653. [Abstract] [Full Text] [PDF] A. Subramanian, S. Hegde, P. Porayette, M. Yon, P. Hankey, and R. F. Paulson Friend Virus Utilizes the BMP4-Dependent Stress Erythropoiesis Pathway To Induce Erythroleukemia J. Virol., January 1, 2008; 82(1): 382 - 393. [Abstract] [Full Text] [PDF] J. Y. Bertrand, A. D. Kim, E. P. Violette, D. L. Stachura, J. L. Cisson, and D. Traver Definitive hematopoiesis initiates through a committed erythromyeloid progenitor in the zebrafish embryo Development, December 1, 2007; 134(23): 4147 - 4156. [Abstract] [Full Text] [PDF] P. Frontelo, D. Manwani, M. Galdass, H. Karsunky, F. Lohmann, P. G. Gallagher, and J. J. Bieker Novel role for EKLF in megakaryocyte lineage commitment Blood, December 1, 2007; 110(12): 3871 - 3880. [Abstract] [Full Text] [PDF] J. Astorga and P. Carlsson Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4 Development, October 15, 2007; 134(20): 3753 - 3761. [Abstract] [Full Text] [PDF] R. C. R. Perlingeiro Endoglin is required for hemangioblast and early hematopoietic development Development, August 15, 2007; 134(16): 3041 - 3048. [Abstract] [Full Text] [PDF] H. K. Bone and M. J. Welham Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis J. Cell Sci., May 15, 2007; 120(10): 1752 - 1762. [Abstract] [Full Text] [PDF] M. Kennedy, S. L. D'Souza, M. Lynch-Kattman, S. Schwantz, and G. Keller Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures Blood, April 1, 2007; 109(7): 2679 - 2687. [Abstract] [Full Text] [PDF] K. Kim, P. Lerou, A. Yabuuchi, C. Lengerke, K. Ng, J. West, A. Kirby, M. J. Daly, and G. Q. Daley Histocompatible Embryonic Stem Cells by Parthenogenesis Science, January 26, 2007; 315(5811): 482 - 486. [Abstract] [Full Text] [PDF] M. Bhatia Hematopoietic Development from Human Embryonic Stem Cells Hematology, January 1, 2007; 2007(1): 11 - 16. [Abstract] [Full Text] [PDF] T. Umemoto, M. Yamato, Y. Shiratsuchi, M. Terasawa, J. Yang, K. Nishida, Y. Kobayashi, and T. Okano Expression of Integrin beta3 Is Correlated to the Properties of Quiescent Hemopoietic Stem Cells Possessing the Side Population Phenotype J. Immunol., December 1, 2006; 177(11): 7733 - 7739. [Abstract] [Full Text] [PDF] H. K. A. Mikkola and S. H. Orkin The journey of developing hematopoietic stem cells. Development, October 1, 2006; 133(19): 3733 - 3744. [Abstract] [Full Text] [PDF] L. Pang, H.-H. Xue, G. Szalai, X. Wang, Y. Wang, D. K. Watson, W. J. Leonard, G. A. Blobel, and M. Poncz Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins Blood, October 1, 2006; 108(7): 2198 - 2206. [Abstract] [Full Text] [PDF] C. Rolny, I. Nilsson, P. Magnusson, A. Armulik, L. Jakobsson, P. Wentzel, P. Lindblom, J. Norlin, C. Betsholtz, R. Heuchel, et al. Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation Blood, September 15, 2006; 108(6): 1877 - 1886. [Abstract] [Full Text] [PDF] M. A. Vodyanik, J. A. Thomson, and I. I. Slukvin Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures Blood, September 15, 2006; 108(6): 2095 - 2105. [Abstract] [Full Text] [PDF] H. Sakamoto, G. Dai, K. Tsujino, K. Hashimoto, X. Huang, T. Fujimoto, M. Mucenski, J. Frampton, and M. Ogawa Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development Blood, August 1, 2006; 108(3): 896 - 903. [Abstract] [Full Text] [PDF] I. Kim, S. He, O. H. Yilmaz, M. J. Kiel, and S. J. Morrison Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors Blood, July 15, 2006; 108(2): 737 - 744. [Abstract] [Full Text] [PDF] S.-i. Takayanagi, T. Hiroyama, S. Yamazaki, T. Nakajima, Y. Morita, J. Usui, K. Eto, T. Motohashi, K. Shiomi, K. Keino-Masu, et al. Genetic marking of hematopoietic stem and endothelial cells: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain Blood, June 1, 2006; 107(11): 4317 - 4325. [Abstract] [Full Text] [PDF] T. Yokota, J. Huang, M. Tavian, Y. Nagai, J. Hirose, J.-C. Zuniga-Pflucker, B. Peault, and P. W. Kincade Tracing the first waves of lymphopoiesis in mice Development, May 15, 2006; 133(10): 2041 - 2051. [Abstract] [Full Text] [PDF] O. H. Yilmaz, M. J. Kiel, and S. J. Morrison SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity Blood, February 1, 2006; 107(3): 924 - 930. [Abstract] [Full Text] [PDF] Z. Li, M. J. Chen, T. Stacy, and N. A. Speck Runx1 function in hematopoiesis is required in cells that express Tek Blood, January 1, 2006; 107(1): 106 - 110. [Abstract] [Full Text] [PDF] Y. Wang, F. Yates, O. Naveiras, P. Ernst, and G. Q. Daley Embryonic stem cell-derived hematopoietic stem cells PNAS, December 27, 2005; 102(52): 19081 - 19086. [Abstract] [Full Text] [PDF] A. Matsubara, A. Iwama, S. Yamazaki, C. Furuta, R. Hirasawa, Y. Morita, M. Osawa, T. Motohashi, K. Eto, H. Ema, et al. Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development J. Exp. Med., December 5, 2005; 202(11): 1483 - 1492. [Abstract] [Full Text] [PDF] H.-F. Lin, D. Traver, H. Zhu, K. Dooley, B. H. Paw, L. I. Zon, and R. I. Handin Analysis of thrombocyte development in CD41-GFP transgenic zebrafish Blood, December 1, 2005; 106(12): 3803 - 3810. [Abstract] [Full Text] [PDF] S. Taoudi, A. M. Morrison, H. Inoue, R. Gribi, J. Ure, and A. Medvinsky Progressive divergence of definitive haematopoietic stem cells from the endothelial compartment does not depend on contact with the foetal liver Development, September 15, 2005; 132(18): 4179 - 4191. [Abstract] [Full Text] [PDF] G. Keller Embryonic stem cell differentiation: emergence of a new era in biology and medicine Genes & Dev., May 15, 2005; 19(10): 1129 - 1155. [Abstract] [Full Text] [PDF] T. M. Schlaeger, H. K. A. Mikkola, C. Gekas, H. B. Helgadottir, and S. H. Orkin Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development Blood, May 15, 2005; 105(10): 3871 - 3874. [Abstract] [Full Text] [PDF] P. U. Magnusson, R. Ronca, P. Dell'Era, P. Carlstedt, L. Jakobsson, J. Partanen, A. Dimberg, and L. Claesson-Welsh Fibroblast Growth Factor Receptor-1 Expression Is Required for Hematopoietic but not Endothelial Cell Development Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 944 - 949. [Abstract] [Full Text] [PDF] J. R. Gothert, S. E. Gustin, M. A. Hall, A. R. Green, B. Gottgens, D. J. Izon, and C. G. Begley In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis Blood, April 1, 2005; 105(7): 2724 - 2732. [Abstract] [Full Text] [PDF] M. A. Vodyanik, J. A. Bork, J. A. Thomson, and I. I. Slukvin Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential Blood, January 15, 2005; 105(2): 617 - 626. [Abstract] [Full Text] [PDF] J. Y. Bertrand, S. Giroux, R. Golub, M. Klaine, A. Jalil, L. Boucontet, I. Godin, and A. Cumano Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin PNAS, January 4, 2005; 102(1): 134 - 139. [Abstract] [Full Text] [PDF] C. I. Baumann, A. S. Bailey, W. Li, M. J. Ferkowicz, M. C. Yoder, and W. H. Fleming PECAM-1 is expressed on hematopoietic stem cells throughout ontogeny and identifies a population of erythroid progenitors Blood, August 15, 2004; 104(4): 1010 - 1016. [Abstract] [Full Text] [PDF] R. K. Burt, L. Verda, D.-A. Kim, Y. Oyama, K. Luo, and C. Link Embryonic Stem Cells As an Alternate Marrow Donor Source: Engraftment without Graft-Versus-Host Disease J. Exp. Med., April 5, 2004; 199(7): 895 - 904. [Abstract] [Full Text] [PDF] W. Li, S. A. Johnson, W. C. Shelley, M. Ferkowicz, P. Morrison, Y. Li, and M. C. Yoder Primary endothelial cells isolated from the yolk sac and para-aortic splanchnopleura support the expansion of adult marrow stem cells in vitro Blood, December 15, 2003; 102(13): 4345 - 4353. [Abstract] [Full Text] [PDF] D. Sugiyama, M. Ogawa, I. Hirose, T. Jaffredo, K.-i. Arai, and K. Tsuji Erythropoiesis from acetyl LDL incorporating endothelial cells at the preliver stage Blood, June 15, 2003; 101(12): 4733 - 4738. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020