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

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. Howev...

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Veröffentlicht in:Stem cells (Dayton, Ohio) Ohio), 2008-01, Vol.26 (1), p.17-29
Hauptverfasser: Tay, Yvonne M.‐S., Tam, Wai‐Leong, Ang, Yen‐Sin, Gaughwin, Philip M., Yang, Henry, Wang, Weijia, Liu, Rubing, George, Joshy, Ng, Huck‐Hui, Perera, Ranjan J., Lufkin, Thomas, Rigoutsos, Isidore, Thomson, Andrew M., Lim, Bing
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container_issue 1
container_start_page 17
container_title Stem cells (Dayton, Ohio)
container_volume 26
creator Tay, Yvonne M.‐S.
Tam, Wai‐Leong
Ang, Yen‐Sin
Gaughwin, Philip M.
Yang, Henry
Wang, Weijia
Liu, Rubing
George, Joshy
Ng, Huck‐Hui
Perera, Ranjan J.
Lufkin, Thomas
Rigoutsos, Isidore
Thomson, Andrew M.
Lim, Bing
description 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.
doi_str_mv 10.1634/stemcells.2007-0295
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Animals
Blotting, Northern
Blotting, Western
Cell differentiation
Cell Differentiation - genetics
Cells, Cultured
DNA-Binding Proteins - metabolism
Embryonic stem cells
Embryonic Stem Cells - cytology
Fluorescent Antibody Technique
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genetic Vectors
Homeodomain Proteins - metabolism
In Situ Hybridization
Mice
MicroRNAs
MicroRNAs - metabolism
Nanog Homeobox Protein
Oligonucleotide Array Sequence Analysis
Receptors, Cytoplasmic and Nuclear - metabolism
Retinoic acid
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Transfection
title MicroRNA‐134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post‐Transcriptional Attenuation of Nanog and LRH1
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