Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD34 / genetics
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Antigens, CD34 / metabolism
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Bone Marrow Cells / cytology
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Cell Differentiation
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Cell Lineage
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Cells, Cultured
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Erythroid Cells / cytology
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Erythroid Cells / metabolism*
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Erythropoietin / pharmacology
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Gene Expression Regulation*
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Genes, Reporter
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / metabolism*
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Humans
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Integrin beta3 / genetics
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Integrin beta3 / metabolism
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K562 Cells
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Megakaryocytes / cytology
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Megakaryocytes / metabolism*
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Mice
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Mice, Inbred C57BL
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Models, Biological
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Platelet Membrane Glycoprotein IIb / genetics
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Platelet Membrane Glycoprotein IIb / metabolism
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Proto-Oncogene Proteins c-myb / antagonists & inhibitors
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Proto-Oncogene Proteins c-myb / genetics
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Thrombopoietin / pharmacology
Substances
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Antigens, CD34
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Integrin beta3
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MicroRNAs
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Platelet Membrane Glycoprotein IIb
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Proto-Oncogene Proteins c-myb
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Erythropoietin
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Thrombopoietin