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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-02-0398. This Article Full Text (PDF) All Versions of this Article: 2002-02-0398v1 101/1/124    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 Liu, B. Articles by Mao, N. Search for Related Content PubMed PubMed Citation Articles by Liu, B. Articles by Mao, N. Social Bookmarking                   What's this? Submitted February 7, 2002 Accepted July 2, 2002 Disruption of Smad5 Gene Leads to Enhanced Proliferation of High Proliferative Potential Precursors During Embryonic Hematopoiesis Bing Liu, Yanxun Sun, Feizi Jiang, Shuangxi Zhang, Ying Wu, Yu Lan, Xiao Yang, and Ning Mao* Cell Biology, Institute of Basic Medical Sciences, Beijing, China Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, China Hematology, Yan Jing Hospital, Beijing, China * Corresponding author; email: maoning{at}nic.bmi.ac.cn. SMAD proteins are downstream signal transducers of the transforming growth factor-ß (TGF-ß) superfamily, which serve as pleiotropic regulators in embryonic and adult hematopoiesis. SMAD5, initially considered to mediate BMP signals, can also transduce the inhibitory signal of TGF-ß1 on proliferation of hematopoietic progenitors derived from human bone marrow. To define its specific role in regulation of primitive multipotential progenitors during early embryonic hematopoiesis, we examined Smad5-/- yolk sacs at E9.0-9.5 and detected elevated number of high proliferative potential colony forming cells (HPP-CFC) with enhanced replating potential. To exclude the possible influence of microenvironmental deficit on embryonic hematopoiesis in vivo, we performed in vitro embryonic stem (ES) cell differentiation assay and investigated the HPP-CFC in particular. Smad5-/- embryoid bodies (EBs) contained elevated number of blast colony forming cells (BL-CFC), the in vitro equivalent of hemangioblast, in contrast with reduced proliferation of primitive erythroid precursors (Ery/P) within the mutant EBs. More importantly, profoundly increased frequency of HPP-CFC, featured with gene dosage effect, was detected within day 6 Smad5-/-M EBs as compared to the wild-type. In addition, Smad5-/- HPP-CFC displayed enhanced self-renewal capacity and decreased sensitivity to TGF-beta1 inhibition, suggesting a critical role of Smad5 in TGF-ß1 regulation of embryonic HPP-CFC. Consistently, RT-PCR analysis detected alterations of the transcription factors including GATA-2 and AML1 as well as cytokine receptors in Smad5-/- HPP-CFC colonies. Together, these data define an important function of SMAD5 in negative regulation of high proliferative potential precursors during embryonic hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Lohmann and J. J. Bieker Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment Development, June 15, 2008; 135(12): 2071 - 2082. [Abstract] [Full Text] [PDF] U. Blank, G. Karlsson, and S. Karlsson Signaling pathways governing stem-cell fate Blood, January 15, 2008; 111(2): 492 - 503. 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