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EMBRYONIC STEM CELLS

MicroRNA-134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post-Transcriptional Attenuation of Nanog and LRH1

^aStem Cell and Developmental Biology, Genome Institute of Singapore, Singapore;
^bBioinformatics Institute, Singapore;
^cInformation and Mathematical Sciences, Genome Institute of Singapore, Singapore;
^dISIS Pharmaceuticals, Carlsbad, California, USA;
^eBioinformatics and Pattern Discovery Group, IBM Thomas J. Watson Research Center, Yorktown Heights, New York, USA;
^fDepartment of Chemical Engineering, Massachusetts Institute of Technology, Boston, Massachusetts, USA;
^gDepartment of Medicine, Harvard Medical School, Boston, Massachusetts, USA

Key Words. Embryonic stem cells • MicroRNAs • Cell differentiation • Retinoic acid

Correspondence: Bing Lim, M.D., Ph.D., Stem Cell and Developmental Biology, Genome Institute of Singapore, #02-01 Genome, Singapore 138672. Telephone: 65-6478-8186; Fax: 65-6478-9005; e-mail: limb1{at}gis.a-star.edu.sg

Received April 23, 2007; accepted for publication September 28, 2007.
First published online in STEM CELLS EXPRESS   October 4, 2007.



Hundreds of microRNAs (miRNAs) are expressed in mammalian cells, where they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. Functional studies to date have demonstrated that several of these miRNAs are important during development. However, the role of miRNAs in the regulation of stem cell growth and differentiation is not well understood. We show herein that microRNA (miR)-134 levels are maximally elevated at day 4 after retinoic acid-induced differentiation or day 2 after N2B27-induced differentiation of mouse embryonic stem cells (mESCs), but this change is not observed during embryoid body differentiation. The elevation of miR-134 levels alone in mESCs enhances differentiation toward ectodermal lineages, an effect that is blocked by a miR-134 antagonist. The promotion of mESC differentiation by miR-134 is due, in part, to its direct translational attenuation of Nanog and LRH1, both of which are known positive regulators of Oct4/POU5F1 and mESC growth. Together, the data demonstrate that miR-134 alone can enhance the differentiation of mESCs to ectodermal lineages and establish a functional role for miR-134 in modulating mESC differentiation through its potential to target and regulate multiple mRNAs.

Disclosure of potential conflicts of interest is found at the end of this article.

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