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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1903-1912. Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-06-093328. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-06-093328v1 111/4/1903    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 CrossRef Google Scholar Articles by Seita, J. Articles by Yoshimoto, T. PubMed PubMed Citation Articles by Seita, J. Articles by Yoshimoto, T. Related Collections Hematopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Interleukin-27 directly induces differentiation in hematopoietic stem cells Jun Seita1, Masayuki Asakawa2,3, Jun Ooehara1, Shin-ichiro Takayanagi1, Yohei Morita4, Nobukazu Watanabe1, Koji Fujita5, Motoshige Kudo5, Junichiro Mizuguchi2,3, Hideo Ema1, Hiromitsu Nakauchi1, and Takayuki Yoshimoto2 1 Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo; 2 Intractable Immune System Disease Research Center and 3 Department of Immunology, Tokyo Medical University, Tokyo; 4 ReproCell, Tokyo; and 5 Department of Pathology, Tokyo Medical University, Tokyo, Japan Interleukin (IL)-27, one of the most recently discovered IL-6 family cytokines, activates both the signal transducer and activator of transcription (STAT)1 and STAT3, and plays multiple roles in pro- and anti-inflammatory immune responses. IL-27 acts on various types of cells including T, B, and macrophage through the common signal-transducing receptor gp130 and its specific receptor WSX-1, but the effect of IL-27 on hematopoietic stem cells (HSCs) remains unknown. Here, we show that IL-27 together with stem cell factor (SCF) directly acts on HSCs and supports their early differentiation in vitro and in vivo. CD34–/lowc-Kit+Sca-1+lineage marker– (CD34–KSL) cells, a population highly enriched in mouse HSCs, were found to express both IL-27 receptor subunits. In vitro cultures of CD34–KSL cells with IL-27 and SCF resulted in an expansion of progenitors including short-term repopulating cells, while some of their long-term repopulating activity also was maintained. To examine its in vivo effect, transgenic mice expressing IL-27 were generated. These mice exhibited enhanced myelopoiesis and impaired B lymphopoiesis in the bone marrow with extramedullary hematopoiesis in the spleen. Moreover, IL-27 similarly acted on human CD34+ cells. These results suggest that IL-27 is one of the limited cytokines that play a role in HSC regulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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