Open AccessMicroRNA‐134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post‐Transcriptional Attenuation of Nanog and LRH1
Author(s) -
Tay Yvonne M.S.,
Tam WaiLeong,
Ang YenSin,
Gaughwin Philip M.,
Yang Henry,
Wang Weijia,
Liu Rubing,
George Joshy,
Ng HuckHui,
Perera Ranjan J.,
Lufkin Thomas,
Rigoutsos Isidore,
Thomson Andrew M.,
Lim Bing
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0295
Subject(s) - biology , homeobox protein nanog , microrna , embryonic stem cell , microbiology and biotechnology , cellular differentiation , stem cell , retinoic acid , embryoid body , genetics , gene , adult stem cell , induced pluripotent stem cell
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.