SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on April 17, 2003; DOI 10.1182/blood-2003-03-0832. This Article 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 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 Related Article in Blood Online Social Bookmarking                   What's this? Submitted March 19, 2003 Accepted March 31, 2003 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* Stem Cell Biology and Regenerative Medicine, Robarts Research Institute, London, ON, Canada; Department of Microbiology, The University of Western Ontario, London, ON, Canada; Department of Physiology, The University of Western Ontario, London, ON, Canada * Corresponding author; email: mbhatia{at}robarts.ca. Human embryonic stem cells (hESC) 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 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: 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] 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] S.-J. Lu, Q. Feng, J. S. Park, L. Vida, B.-S. Lee, M. Strausbauch, P. J. Wettstein, G. R. Honig, and R. Lanza Biologic properties and enucleation of red blood cells from human embryonic stem cells Blood, December 1, 2008; 112(12): 4475 - 4484. [Abstract] [Full Text] [PDF] Z. Su, C. Frye, K.-M. Bae, V. Kelley, and J. Vieweg Differentiation of Human Embryonic Stem Cells into Immunostimulatory Dendritic Cells under Feeder-Free Culture Conditions Clin. Cancer Res., October 1, 2008; 14(19): 6207 - 6217. [Abstract] [Full Text] [PDF] C. H. Martin, P. S. Woll, Z. Ni, J. C. Zuniga-Pflucker, and D. S. Kaufman Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells Blood, October 1, 2008; 112(7): 2730 - 2737. [Abstract] [Full Text] [PDF] C. M. Cameron, F. Harding, W.-S. Hu, and D. S. Kaufman Activation of Hypoxic Response in Human Embryonic Stem Cell-Derived Embryoid Bodies Experimental Biology and Medicine, August 1, 2008; 233(8): 1044 - 1057. [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] K.-M. Chan, S. Bonde, H. Klump, and N. Zavazava Hematopoiesis and immunity of HOXB4-transduced embryonic stem cell-derived hematopoietic progenitor cells Blood, March 15, 2008; 111(6): 2953 - 2961. [Abstract] [Full Text] [PDF] W. E. Lowry, L. Richter, R. Yachechko, A. D. Pyle, J. Tchieu, R. Sridharan, A. T. Clark, and K. Plath Generation of human induced pluripotent stem cells from dermal fibroblasts PNAS, February 26, 2008; 105(8): 2883 - 2888. [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] P. Zhang, J. Li, Z. Tan, C. Wang, T. Liu, L. Chen, J. Yong, W. Jiang, X. Sun, L. Du, et al. Short-term BMP-4 treatment initiates mesoderm induction in human embryonic stem cells Blood, February 15, 2008; 111(4): 1933 - 1941. [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] L. J. McReynolds, S. Gupta, M. E. Figueroa, M. C. Mullins, and T. Evans Smad1 and Smad5 differentially regulate embryonic hematopoiesis Blood, December 1, 2007; 110(12): 3881 - 3890. [Abstract] [Full Text] [PDF] S. Levenberg, J. Zoldan, Y. Basevitch, and R. Langer Endothelial potential of human embryonic stem cells Blood, August 1, 2007; 110(3): 806 - 814. [Abstract] [Full Text] [PDF] K. E. Sullivan, A. B. M. Reddy, K. Dietzmann, A. R. Suriano, V. P. Kocieda, M. Stewart, and M. Bhatia Epigenetic Regulation of Tumor Necrosis Factor Alpha Mol. Cell. Biol., July 15, 2007; 27(14): 5147 - 5160. [Abstract] [Full Text] [PDF] N. L. Boyd, S. K. Dhara, R. Rekaya, E. A. Godbey, K. Hasneen, R. R. Rao, F. D. West III, B. A. Gerwe, and S. L. Stice BMP4 Promotes Formation of Primitive Vascular Networks in Human Embryonic Stem Cell-Derived Embryoid Bodies Experimental Biology and Medicine, June 1, 2007; 232(6): 833 - 843. [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] T. Nakayama, N. Mutsuga, and G. Tosato Effect of Fibroblast Growth Factor 2 on Stromal Cell-Derived Factor 1 Production by Bone Marrow Stromal Cells and Hematopoiesis J Natl Cancer Inst, February 7, 2007; 99(3): 223 - 235. [Abstract] [Full Text] [PDF] J. E. Pimanda, I. J. Donaldson, M. F. T. R. de Bruijn, S. Kinston, K. Knezevic, L. Huckle, S. Piltz, J.-R. Landry, A. R. Green, D. Tannahill, et al. The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity PNAS, January 16, 2007; 104(3): 840 - 845. [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] S. Singbrant, J. L. Moody, U. Blank, G. Karlsson, L. Umans, A. Zwijsen, and S. Karlsson Smad5 is dispensable for adult murine hematopoiesis Blood, December 1, 2006; 108(12): 3707 - 3712. [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. E. Fleming and D. T. Scadden Embryonic stem cells make human T cells PNAS, August 15, 2006; 103(33): 12213 - 12214. [Full Text] [PDF] Z. Galic, S. G. Kitchen, A. Kacena, A. Subramanian, B. Burke, R. Cortado, and J. A. Zack From the Cover: T lineage differentiation from human embryonic stem cells PNAS, August 1, 2006; 103(31): 11742 - 11747. [Abstract] [Full Text] [PDF] L. Armstrong, O. Hughes, S. Yung, L. Hyslop, R. Stewart, I. Wappler, H. Peters, T. Walter, P. Stojkovic, J. Evans, et al. The role of PI3K/AKT, MAPK/ERK and NF{kappa}{beta} signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis Hum. Mol. Genet., June 1, 2006; 15(11): 1894 - 1913. [Abstract] [Full Text] [PDF] A. Trounson The Production and Directed Differentiation of Human Embryonic Stem Cells Endocr. Rev., April 1, 2006; 27(2): 208 - 219. [Abstract] [Full Text] [PDF] M. W. Lensch and G. Q. Daley Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells Blood, April 1, 2006; 107(7): 2605 - 2612. [Abstract] [Full Text] [PDF] I. I. Slukvin, M. A. Vodyanik, J. A. Thomson, M. E. Gumenyuk, and K.-D. Choi Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway. J. Immunol., March 1, 2006; 176(5): 2924 - 2932. [Abstract] [Full Text] [PDF] A. D. Narayan, J. L. Chase, R. L. Lewis, X. Tian, D. S. Kaufman, J. A. Thomson, and E. D. Zanjani Human embryonic stem cell-derived hematopoietic cells are capable of engrafting primary as well as secondary fetal sheep recipients Blood, March 1, 2006; 107(5): 2180 - 2183. [Abstract] [Full Text] [PDF] A. L. Olsen, D. L. Stachura, and M. J. Weiss Designer blood: creating hematopoietic lineages from embryonic stem cells Blood, February 15, 2006; 107(4): 1265 - 1275. [Abstract] [Full Text] [PDF] H. Zhang, K. Saeki, A. Kimura, K. Saeki, M. Nakahara, M. Doshi, Y. Kondo, T. Nakano, and A. Yuo Efficient and Repetitive Production of Hematopoietic and Endothelial Cells from Feeder-Free Monolayer Culture System of Primate Embryonic Stem Cells Biol Reprod, February 1, 2006; 74(2): 295 - 306. [Abstract] [Full Text] [PDF] P. S. Woll, C. H. Martin, J. S. Miller, and D. S. Kaufman Human Embryonic Stem Cell-Derived NK Cells Acquire Functional Receptors and Cytolytic Activity J. Immunol., October 15, 2005; 175(8): 5095 - 5103. [Abstract] [Full Text] [PDF] E. S. Ng, R. P. Davis, L. Azzola, E. G. Stanley, and A. G. Elefanty Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation Blood, September 1, 2005; 106(5): 1601 - 1603. [Abstract] [Full Text] [PDF] E. T. Zambidis, B. Peault, T. S. Park, F. Bunz, and C. I. Civin Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development Blood, August 1, 2005; 106(3): 860 - 870. [Abstract] [Full Text] [PDF] L. Wang, L. Li, P. Menendez, C. Cerdan, and M. Bhatia Human embryonic stem cells maintained in the absence of mouse embryonic fibroblasts or conditioned media are capable of hematopoietic development Blood, June 15, 2005; 105(12): 4598 - 4603. [Abstract] [Full Text] [PDF] L. Lagostena, D. Avitabile, E. De Falco, A. Orlandi, F. Grassi, M. G. Iachininoto, G. Ragone, S. Fucile, G. Pompilio, F. Eusebi, et al. Electrophysiological properties of mouse bone marrow c-kit+ cells co-cultured onto neonatal cardiac myocytes Cardiovasc Res, June 1, 2005; 66(3): 482 - 492. [Abstract] [Full Text] [PDF] L. Wang, P. Menendez, F. Shojaei, L. Li, F. Mazurier, J. E. Dick, C. Cerdan, K. Levac, and M. Bhatia Generation of hematopoietic repopulating cells from human embryonic stem cells independent of ectopic HOXB4 expression J. Exp. Med., May 16, 2005; 201(10): 1603 - 1614. [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] 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] M. F. Pera and A. O. Trounson Human embryonic stem cells: prospects for development Development, November 15, 2004; 131(22): 5515 - 5525. [Abstract] [Full Text] [PDF] S.-J. Lu, F. Li, L. Vida, and G. R. Honig CD34+CD38- hematopoietic precursors derived from human embryonic stem cells exhibit an embryonic gene expression pattern Blood, June 1, 2004; 103(11): 4134 - 4141. [Abstract] [Full Text] [PDF] K. Umeda, T. Heike, M. Yoshimoto, M. Shiota, H. Suemori, H. Y. Luo, D. H. K. Chui, R. Torii, M. Shibuya, N. Nakatsuji, et al. Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro Development, April 15, 2004; 131(8): 1869 - 1879. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020