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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 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 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 Liu, B. Articles by Mao, N. Search for Related Content PubMed PubMed Citation Articles by Liu, B. Articles by Mao, N. Related Collections Hematopoiesis and Stem Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 124-133 HEMATOPOIESIS 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 From the Department of Cell Biology, Institute of Basic Medical Sciences, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, and Department of Hematology, Yan Jing Hospital, Beijing, Peoples' Republic of China. SMAD proteins are downstream signal transducers of the transforming growth factor  (TGF-) superfamily, which serve as pleiotropic regulators in embryonic and adult hematopoiesis. SMAD5, initially considered to mediate bone morphogenetic proteins (BMPs) signals, can also transduce the inhibitory signal of TGF-1 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 to 9.5 and detected an elevated number of high-proliferative potential colony-forming cells (HPP-CFCs) 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-CFCs in particular. Smad5/ embryoid bodies (EBs) contained an elevated number of blast colony-forming cells (BL-CFCs), the in vitro equivalent of hemangioblast, in contrast to reduced proliferation of primitive erythroid precursors (Ery/Ps) within the mutant EBs. More importantly, profoundly increased frequency of HPP-CFCs, featured with a gene-dosage effect, was detected within day 6 Smad5/ EBs compared with the wild type. In addition, Smad5/ HPP-CFCs displayed enhanced self-renewal capacity and decreased sensitivity to TGF-1 inhibition, suggesting a critical role of Smad5 in TGF-1 regulation of embryonic HPP-CFCs. Consistently, reverse transcription-polymerase chain reaction 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. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Lohmann and J. J. 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