MicroRNA-mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors

Dev Cell. 2008 Jun;14(6):843-53. doi: 10.1016/j.devcel.2008.03.012.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism*
  • Erythropoietin / pharmacology
  • Gene Expression Regulation*
  • Genes, Reporter
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Integrin beta3 / genetics
  • Integrin beta3 / metabolism
  • K562 Cells
  • Megakaryocytes / cytology
  • Megakaryocytes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Biological
  • Platelet Membrane Glycoprotein IIb / genetics
  • Platelet Membrane Glycoprotein IIb / metabolism
  • Proto-Oncogene Proteins c-myb / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myb / genetics
  • Thrombopoietin / pharmacology

Substances

  • Antigens, CD34
  • Integrin beta3
  • MicroRNAs
  • Platelet Membrane Glycoprotein IIb
  • Proto-Oncogene Proteins c-myb
  • Erythropoietin
  • Thrombopoietin

Associated data

  • GEO/GSE10593