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. 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.
Tay
Yvonne M-S
YM
Stem Cell and Developmental Biology, Genome Institute of Singapore, #02-01 Genome, Singapore 138672.
Tam
Wai-Leong
WL
Ang
Yen-Sin
YS
Gaughwin
Philip M
PM
Yang
Henry
H
Wang
Weijia
W
Liu
Rubing
R
George
Joshy
J
Ng
Huck-Hui
HH
Perera
Ranjan J
RJ
Lufkin
Thomas
T
Rigoutsos
Isidore
I
Thomson
Andrew M
AM
Lim
Bing
B
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D020411:Oligonucleotide Array Sequence Analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear