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Prepublished online as a Blood First Edition Paper on April 17, 2003; DOI 10.1182/blood-2003-03-0832. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0832v1 102/3/906    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 Chadwick, K. Articles by Bhatia, M. Search for Related Content PubMed PubMed Citation Articles by Chadwick, K. Articles by Bhatia, M. Related Collections Hematopoiesis and Stem Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 906-915 HEMATOPOIESIS Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells Kristin Chadwick, Lisheng Wang, Li Li, Pablo Menendez, Barbara Murdoch, Anne Rouleau, and Mickie Bhatia From the Robarts Research Institute, Stem Cell Biology and Regenerative Medicine; and the Departments of Microbiology and Immunology and Physiology, University of Western Ontario, London, ON, Canada Human embryonic stem cells (hESCs) randomly differentiate into multiple cell types during embryoid body (EB) development. To date, characterization of specific factors capable of influencing hematopoietic cell fate from hESCs remains elusive. Here, we report that the treatment of hESCs during EB development with a combination of cytokines and bone morphogenetic protein-4 (BMP-4), a ventral mesoderm inducer, strongly promotes hematopoietic differentiation. Hematopoietic progenitors of multiple lineages were generated from EBs and were found to be restricted to the population of progeny expressing cell surface CD45. Addition of BMP-4 had no statistically significant effect on hematopoietic differentiation but enabled significant enhancement in progenitor self-renewal, independent of cytokine treatment. Hematopoietic commitment was characterized as the temporal emergence of single CD45+ cells first detectable after day 10 of culture and was accompanied by expression of hematopoietic transcription factors. Despite the removal of cytokines at day 10, hematopoietic differentiation of hESCs continued, suggesting that cytokines act on hematopoietic precursors as opposed to differentiated hematopoietic cells. Our study establishes the first evidence for the role of cytokines and BMP-4 in promoting hematopoietic differentiation of hESC lines and provides an unprecedented system to study early developmental events that govern the initiation of hematopoiesis in the human. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: ESCs and hematopoietic fate: mixing the perfect "cocktail" Kimberly A Dooley and Leonard I. Zon Blood 2003 102: 776. [Full Text] [PDF] This article has been cited by other articles: Y. Yokoyama, T. Suzuki, M. Sakata-Yanagimoto, K. Kumano, K. Higashi, T. Takato, M. Kurokawa, S. Ogawa, and S. Chiba Derivation of functional mature neutrophils from human embryonic stem cells Blood, June 25, 2009; 113(26): 6584 - 6592. [Abstract] [Full Text] [PDF] Z. Galic, S. G. Kitchen, A. Subramanian, G. Bristol, M. D. Marsden, A. Balamurugan, A. Kacena, O. Yang, and J. A. 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