Specific microRNAs modulate embryonic stem cell-derived neurogenesis.
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.
Krichevsky
Anna M
AM
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. krichevsky@cnd.bwh.harvard.edu
Sonntag
Kai-C
KC
Isacson
Ole
O
Kosik
Kenneth S
KS
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D020869:Gene Expression Profiling; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D039901:Totipotent Stem Cells / Q000166:cytology* / Q000378:metabolism*
D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse