MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors

Okuyama K.; Ikawa T.; Gentner B.Hozumi K.Harnprasopwat R.Lu J.Yamashita R.Ha D.Toyoshima T.Chanda B.Kawamata T.Yokoyama K.Wang S.Ando K.Lodish H.F.Tojo A.Kawamoto H.Kotani A.

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MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors

机译：MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors

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Lineage specification is thought to be largely regulated at the level of transcription, where lineage-specific transcription factors drive specific cell fates. MicroRNAs (miR), vital to many cell functions, act posttranscriptionally to decrease the expression of target mRNAs. MLL-AF4 acute lymphocytic leukemia exhibits both myeloid and B-cell surface markers, suggesting that the transformed cells are Bcell myeloid progenitor cells. Through gain- and loss-of-function experiments, we demonstrated that microRNA 126 (miR-126) drives B-cell myeloid biphenotypic leukemia differentiation toward B cells without changing expression of E2A immunoglobulin enhancerbinding factor E12/E47 (E2A), early B-cell factor 1 (EBF1), or paired box protein 5, which are critical transcription factors in B-lymphopoiesis. Similar induction of B-cell differentiation by miR-126 was observed in normal hematopoietic cells in vitro and in vivo in uncommitted murine c-Kit+Sca1+Lineage- cells, with insulin regulatory subunit-1 acting as a target of miR-126. Importantly, in EBF1- deficient hematopoietic progenitor cells, which fail to differentiate into B cells, miR-126 significantly up-regulated B220, and induced the expression of B-cell genes, including recombination activating genes-1/2 and CD79a/b. These data suggest that miR-126 can at least partly rescue B-cell development independently of EBF1. These experiments show that miR-126 regulates myeloid vs. B-cell fate through an alternative machinery, establishing the critical role of miRNAs in the lineage specification of multipotent mammalian cells.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第33期|13410-13415|共6页
作者
Okuyama K.; Ikawa T.; Gentner B.Hozumi K.Harnprasopwat R.Lu J.Yamashita R.Ha D.Toyoshima T.Chanda B.Kawamata T.Yokoyama K.Wang S.Ando K.Lodish H.F.Tojo A.Kawamoto H.Kotani A.;
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作者单位

Division of Hematological Malignancy, Regenerative Medical Science, Tokai University School of Medicine, Kanagawa 259-1193, Japan;

RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan;

San Raffaele Scientific Institute, 20123 Milan, ItalyDepartment of Immunology, Tokai University School of Medicine, Kanagawa 259-1193, JapanInstitute of Medical Science, University of Tokyo, Tokyo 108-8639, JapanDepartment of Hematology, Tokai University, Kanagawa 259-1193, JapanTufts University School of Medicine, Boston, MA 02111, United StatesTulane University, New Orleans, LA 70118, United StatesWhitehead Institute for Biomedical Research, Cambridge, MA 02142, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cell fate decision; Lymphopoiesis;

MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors

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