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Dev Cell DOI:10.1016/j.devcel.2008.03.012

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
JournalDev Cell
Date Published2008 Jun
KeywordsAnimals, Antigens, CD34, Bone Marrow Cells, Cell Differentiation, Cell Lineage, Cells, Cultured, Erythroid Cells, Erythropoietin, Gene Expression Regulation, Genes, Reporter, Hematopoietic Stem Cells, Humans, Integrin beta3, K562 Cells, Megakaryocytes, Mice, Mice, Inbred C57BL, MicroRNAs, Models, Biological, Platelet Membrane Glycoprotein IIb, Proto-Oncogene Proteins c-myb, Thrombopoietin

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.


Alternate JournalDev. Cell
PubMed ID18539114
PubMed Central IDPMC2688789
Grant List / / Howard Hughes Medical Institute / United States