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This Article Full Text Full Text (PDF) 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 Bunting, K. D. Articles by Ihle, J. N. Search for Related Content PubMed PubMed Citation Articles by Bunting, K. D. Articles by Ihle, J. N. Related Collections Hematopoiesis and Stem Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 January 2002, Vol. 99, No. 2, pp. 479-487 HEMATOPOIESIS Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5 Kevin D. Bunting, Heath L. Bradley, Teresa S. Hawley, Richard Moriggl, Brian P. Sorrentino, and James N. Ihle From the Hematopoiesis Department, American Red Cross Holland Laboratory, Rockville, MD; the Research Institute of Molecular Pathology, Vienna, Austria; the Division of Experimental Hematology and the Biochemistry Department, St Jude Children's Research Hospital, Memphis, TN; and the Howard Hughes Medical Institute, Chevy Chase, MD. Signal transducers and activators of transcription (STATs) are intracellular mediators of cytokine receptor signals. Because many early-acting growth factors have been implicated in STAT5 activation, this study sought to investigate whether STAT5 may be a transcriptional regulator of hematopoietic stem cell (HSC) long-term repopulating activity. To test this possibility, bone marrow (BM) and fetal liver (FL) cells from mice containing homozygous deletions of both STAT5a and STAT5b genes (STAT5ab/) were characterized for hematopoietic repopulating activities. BM and FL grafts were capable of repopulating lymphoid and myeloid lineages of lethally irradiated primary and secondary hosts, with defects observed primarily in T-lymphocyte engraftment. Because only a fraction of normal HSC function is required to reconstitute hematopoiesis, competitive repopulation assays of adult BM or FL cells were used against wild type adult BM or FL cells to quantitate stem cell function. In these analyses, average 25-, 28-, 45-, and 68-fold decreases in normal repopulating activity were evident in granulocyte (Gr-1+), macrophage (Mac-1+), erythroid progenitor (Ter119+), and B-lymphocyte (B220+) populations, respectively, with T lymphocytes (CD4+) always undetectable from the STAT5ab/ graft. Consistent with previous reports of divergence between stem cell phenotype and function in cases of perturbed hematopoiesis, the absolute number of cells within Sca-1+c-kit+lin or lin Hoechst 33342 side population fractions was not significantly different between wild type and STAT5ab/ BM or FL cells. These results demonstrate that a significant proportion of the growth factor signals required for multilineage reconstitution potential of HSCs is STAT5 dependent. © 2002 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. G. Olthof, S. Fatrai, A. L. Drayer, M. R. Tyl, E. Vellenga, and J. J. Schuringa Downregulation of Signal Transducer and Activator of Transcription 5 (STAT5) in CD34+ Cells Promotes Megakaryocytic Development, Whereas Activation of STAT5 Drives Erythropoiesis Stem Cells, July 1, 2008; 26(7): 1732 - 1742. [Abstract] [Full Text] [PDF] D. Kent, M. 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