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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6440-6448. Prepublished online as a Blood First Edition Paper on April 20, 2009; DOI 10.1182/blood-2008-09-171728. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-09-171728v1 113/25/6440    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 Bhatia, H. Articles by Little, J. A. PubMed PubMed Citation Articles by Bhatia, H. Articles by Little, J. A. Related Collections Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS Short-chain fatty acid–mediated effects on erythropoiesis in primary definitive erythroid cells Himanshu Bhatia1, Jennifer L. Hallock2, Amrita Dutta1, Shay Karkashon1, Lauren S. Sterner2, Toru Miyazaki3, Ann Dean2, and Jane A. Little1 1 Division of Hematology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; 2 Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; and 3 Division of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan Short-chain fatty acids (SCFAs; butyrate and propionate) up-regulate embryonic/fetal globin gene expression through unclear mechanisms. In a murine model of definitive erythropoiesis, SCFAs increased embryonic β-type globin gene expression in primary erythroid fetal liver cells (eFLCs) after 72 hours in culture, from 1.7% (± 1.2%) of total β-globin gene expression at day 0 to 4.9% (± 2.2%) in propionate and 5.4% (± 3.4%) in butyrate; this effect was greater in butyrate plus insulin/erythropoietin (BIE), at 19.5% (± 8.3%) compared with 0.1% (± 0.1%) in ins/EPO alone (P < .05). Fetal -globin gene expression was increased in human transgene-containing eFLCs, to 35.9% (± 7.0%) in BIE compared with 4.4% (± 4.2%) in ins/EPO only (P < .05). Embryonic globin gene expression was detectable in 11 of 15 single eFLCs treated with BIE, but in0 of 15 ins/EPO-only treated cells. Butyrate-treated [65.5% (± 9.9%)] and 77.5% (± 4.0%) propionate-treated eFLCs were highly differentiated in culture, compared with 21.5% (± 3.5%) in ins/EPO (P < .005). Importantly, signaling intermediaries, previously implicated in induced embryonic/fetal globin gene expression (STAT5, p42/44, and p38), were not differentially activated by SCFAs in eFLCs; but increased bulk histone (H3) acetylation was seen in SCFA-treated eFLCs. SCFAs induce embryonic globin gene expression in eFLCS, which are a useful short-term and physiologic primary cell model of embryonic/fetal globin gene induction during definitive erythropoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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