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Developmental Cell DOI:

MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors

Publication TypeJournal Article
Year of Publication2008
AuthorsLu, J, Guo, S, Ebert, BL, Zhang, H, Peng, X, Bosco, J, Pretz, J, Schlanger, R, Wang, JY, Mak, RH, Dombkowski, DM, Preffer, FI, Scadden, DT, Golub, TR
JournalDevelopmental Cell
Pages843 - 53
Date Published2008/06//
ISBN Number1534-5807
KeywordsAnimals, Antigens, Bone Marrow Cells, Cancer, CD34, Cell Differentiation, Cell Lineage, Cells, Cultured, Erythroid Cells, Erythropoietin, Gene Expression Regulation, Genes, Hematopoietic Stem Cells, Humans, Integrin beta3, K562 Cells, Megakaryocytes, Mi, Reporter

Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in those processes and used the poorly understood regulation of megakaryocyte-erythrocyte progenitors (MEPs) in hematopoiesis as a model system. We report here that miR-150 modulates lineage fate in MEPs. Using a novel methodology capable of profiling miRNA expression in small numbers of primary cells, we identify miR-150 as preferentially expressed in the megakaryocytic lineage. Through gain- and loss-of-function experiments, we demonstrate that miR-150 drives MEP differentiation toward megakaryocytes at the expense of erythroid cells in vitro and in vivo. Moreover, we identify the transcription factor MYB as a critical target of miR-150 in this regulation. These experiments show that miR-150 regulates MEP fate, and thus establish a role for miRNAs in lineage specification of mammalian multipotent cells.