Specific microRNAs modulate embryonic stem cell-derived neurogenesis

Stem Cells. 2006 Apr;24(4):857-64. doi: 10.1634/stemcells.2005-0441. Epub 2005 Dec 15.

Abstract

MicroRNAs (miRNAs) are recently discovered small non-coding transcripts with a broad spectrum of functions described mostly in invertebrates. As post-transcriptional regulators of gene expression, miRNAs trigger target mRNA degradation or translational repression. Although hundreds of miRNAs have been cloned from a variety of mammalian tissues and cells and multiple mRNA targets have been predicted, little is known about their functions. So far, a role of miRNA has only been described in hematopoietic, adipocytic, and muscle differentiation; regulation of insulin secretion; and potentially regulation of cancer growth. Here, we describe miRNA expression profiling in mouse embryonic stem (ES) cell- derived neurogenesis in vitro and show that a number of miRNAs are simultaneously co-induced during differentiation of neural progenitor cells to neurons and astrocytes. There was a clear correlation between miRNA expression profiles in ES cell-derived neurogenesis in vitro and in embryonal neurogenesis in vivo. Using both gain-of-function and loss-of-function approaches, we demonstrate that brain-specific miR-124a and miR-9 molecules affect neural lineage differentiation in the ES cell-derived cultures. In addition, we provide evidence that signal transducer and activator of transcription (STAT) 3, a member of the STAT family pathway, is involved in the function of these miRNAs. We conclude that distinct miRNAs play a functional role in the determination of neural fates in ES cell differentiation.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • Gene Expression Profiling
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Neurons / cytology*
  • Neurons / metabolism*
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism
  • Totipotent Stem Cells / cytology*
  • Totipotent Stem Cells / metabolism*

Substances

  • MicroRNAs
  • STAT3 Transcription Factor
  • Stat3 protein, mouse