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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3097-3105. Prepublished online as a Blood First Edition Paper on July 13, 2004; DOI 10.1182/blood-2004-03-1224. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1224v1 104/10/3097    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 Hadland, B. K. Articles by Longmore, G. D. Search for Related Content PubMed PubMed Citation Articles by Hadland, B. K. Articles by Longmore, G. D. Related Collections Hematopoiesis and Stem Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development Brandon K. Hadland, Stacey S. Huppert, Jyotshnabala Kanungo, Yingzi Xue, Rulang Jiang, Thomas Gridley, Ronald A. Conlon, Alec M. Cheng, Raphael Kopan, and Gregory D. Longmore From the Departments of Medicine and Cell Biology, Molecular Biology and Pharmacology, and Medicine and Immunology, Washington University School of Medicine, St Louis, MO; The Jackson Laboratory, Bar Harbor, ME; the Department of Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH. Notch1 is known to play a critical role in regulating fates in numerous cell types, including those of the hematopoietic lineage. Multiple defects exhibited by Notch1-deficient embryos confound the determination of Notch1 function in early hematopoietic development in vivo. To overcome this limitation, we examined the developmental potential of Notch1–/– embryonic stem (ES) cells by in vitro differentiation and by in vivo chimera analysis. Notch1 was found to affect primitive erythropoiesis differentially during ES cell differentiation and in vivo, and this result reflected an important difference in the regulation of Notch1 expression during ES cell differentiation relative to the developing mouse embryo. Notch1 was dispensable for the onset of definitive hematopoiesis both in vitro and in vivo in that Notch1–/– definitive progenitors could be detected in differentiating ES cells as well as in the yolk sac and early fetal liver of chimeric mice. Despite the fact that Notch1–/– cells can give rise to multiple types of definitive progenitors in early development, Notch1–/– cells failed to contribute to long-term definitive hematopoiesis past the early fetal liver stage in the context of a wild-type environment in chimeric mice. Thus, Notch1 is required, in a cell-autonomous manner, for the establishment of long-term, definitive hematopoietic stem cells (HSCs). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] M. Stahl, K. Uemura, C. Ge, S. Shi, Y. Tashima, and P. Stanley Roles of Pofut1 and O-Fucose in Mammalian Notch Signaling J. Biol. 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