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Specific microRNAs modulate embryonic stem cell-derived neurogenesis.

Krichevsky, Anna M., Sonntag, Kai-C., Isacson, Ole, Kosik, Kenneth S.·2006·Stem Cells
DOI 10.1634/stemcells.2005-0441
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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.

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Authors
Krichevsky, A. M., Sonntag, K.-C., Isacson, O., & Kosik, K. S.
Affiliations
  • Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  • Center for Neuroregeneration Research, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA
  • Neuroscience Research Institute, University of California-Santa Barbara, Santa Barbara, California, USA
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2006-04-01
Volume
24
Issue
4
Pages
857-864
ISSN
  • 1066-5099
  • 1549-4918
DOI
10.1634/stemcells.2005-0441
Cited by
574
References
4
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)

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