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Related Collections Hematopoiesis and Stem Cells Cell Cycle Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2001, Vol. 98, No. 13, pp. 3643-3649 HEMATOPOIESIS Transforming growth factor 1 mediates cell-cycle arrest of primitive hematopoietic cells independent of p21Cip1/Waf1 or p27Kip1 Tao Cheng, Hongmei Shen, Neil Rodrigues, Sebastian Stier, and David T. Scadden From the MGH Cancer Center and AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, and Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA. The regulation of stem cell proliferation is a poorly understood process balancing rapid, massive blood cell production in times of stress with maintenance of a multipotent stem cell pool over decades of life. Transforming growth factor 1 (TGF-1) has pleiotropic effects on hematopoietic cells, including the inhibition of primitive cell proliferation. It was recently demonstrated that the cyclin-dependent kinase inhibitors, p21Cip1/Waf1 (p21) and p27Kip1 (p27), can inhibit the proliferation of hematopoietic stem cells and progenitor cells, respectively. The relation of TGF-1 stimulation to p21 and p27 was examined using a fine-mapping approach to gene expression in individual cells. Abundant TGF-1 expression and p21 expression were documented in quiescent, cytokine-resistant hematopoietic stem cells and in terminally differentiated mature blood cells, but not in proliferating progenitor cell populations. TGF-1 receptor (TR II) was expressed ubiquitously without apparent modulation. Cell- cycle-synchronized 32D cells exposed to TGF-1 demonstrated a marked antiproliferative effect of TGF-1, yet neither the level of p21 mRNA nor the protein level of either p21 or p27 was altered. To corroborate these observations in primary cells, bone marrow mononuclear cells derived from mice engineered to be deficient in p21 or p27 were assessed. Progenitor and primitive cell function was inhibited by TGF-1 equivalently in / and +/+ littermate controls. These data indicate that TGF-1 exerts its inhibition on cell cycling independent of p21 and p27 in hematopoietic cells. TGF-1 and p21 or p27 participate in independent pathways of stem cell regulation, suggesting that targeting each may provide complementary strategies for enhancing stem or progenitor cell expansion and gene transduction. © 2001 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: S. Yamazaki, A. Iwama, S.-i. Takayanagi, K. Eto, H. Ema, and H. 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