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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-04-1300. This Article Full Text (PDF) All Versions of this Article: 2003-04-1300v1 102/9/3129    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 Larsson, J. Articles by Karlsson, S. Search for Related Content PubMed PubMed Citation Articles by Larsson, J. Articles by Karlsson, S. Social Bookmarking                   What's this? Submitted April 29, 2003 Accepted June 23, 2003 TGF- signaling-deficient hematopoietic stem cells have normal self-renewal and regenerative ability in vivo despite increased proliferative capacity in vitro Jonas Larsson*, Ulrika Blank, Hildur Helgadottir, Jon Mar Bjornsson, Mats Ehinger, Marie-Jose Goumans, Xiaolong Fan, Per Leveen, and Stefan Karlsson Department of Molecular Medicine and Gene Therapy, Lund Unversity, Lund, Sweden Department of Pathology, Lund Unversity, Lund, Sweden Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands * Corresponding author; email: jonas.larsson{at}molmed.lu.se. Studies in vitro implicate TGF- as a key regulator of hematopoiesis with potent inhibitory effects on progenitor and stem cell proliferation. In vivo studies have been hampered by early lethality of knockout mice for TGF- isoforms and the receptors. In order to directly assess the role of TGF- signaling for hematopoiesis and hematopoietic stem cell (HSC) function in vivo, we generated a conditional knockout model in which a disruption of the TGF- type I receptor (TRI) gene was induced in adult mice. HSCs from induced mice showed increased proliferation recruitment when cultured as single cells under low stimulatory conditions in vitro, consistent with an inhibitory role of TGF- in HSC proliferation. However, induced TRI null mice show normal in vivo hematopoiesis with normal numbers and differentiation ability of hematopoietic progenitor cells. Furthermore HSCs from TRI null mice exhibit a normal cell cycle distribution and do not differ in their ability to long term repopulate primary and secondary recipient mice following bone marrow transplantation. These findings challenge the classical view that TGF- is an essential negative regulator of hematopoietic stem cells under physiological conditions in vivo. 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