miR-17 Family miRNAs Are Expressed During Early Mammalian Development and Regulate Stem Cell Differentiation

Dev Biol. 2009 Feb 15;326(2):431-43. doi: 10.1016/j.ydbio.2008.11.016. Epub 2008 Dec 3.

Abstract

MicroRNAs are small non-coding RNAs that regulate protein expression by binding 3'UTRs of target mRNAs, thereby inhibiting translation. Similar to siRNAs, miRNAs are cleaved by Dicer. Mouse and ES cell Dicer mutants demonstrate that microRNAs are necessary for embryonic development and cellular differentiation. However, technical obstacles and the relative infancy of this field have resulted in few data on the functional significance of individual microRNAs. We present evidence that miR-17 family members, miR-17-5p, miR-20a, miR-93, and miR-106a, are differentially expressed in developing mouse embryos and function to control differentiation of stem cells. Specifically, miR-93 localizes to differentiating primitive endoderm and trophectoderm of the blastocyst. We also observe high miR-93 and miR-17-5p expression within the mesoderm of gastrulating embryos. Using an ES cell model system, we demonstrate that modulation of these miRNAs delays or enhances differentiation into the germ layers. Additionally, we demonstrate that these miRNAs regulate STAT3 mRNA in vitro. We suggest that STAT3, a known ES cell regulator, is one target mRNA responsible for the effects of these miRNAs on cellular differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Blastocyst / cytology
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / physiology*
  • Female
  • Fetal Proteins / genetics
  • Fetal Proteins / metabolism
  • Fibroblast Growth Factor 5 / genetics
  • Fibroblast Growth Factor 5 / metabolism
  • Hepatocyte Nuclear Factor 4 / genetics
  • Hepatocyte Nuclear Factor 4 / metabolism
  • In Situ Hybridization
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Morphogenesis*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • Fetal Proteins
  • Fgf5 protein, mouse
  • Hepatocyte Nuclear Factor 4
  • Hnf4a protein, mouse
  • MicroRNAs
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • T-Box Domain Proteins
  • Fibroblast Growth Factor 5
  • Brachyury protein