Genome-wide identification of microRNA targets in human ES cells reveals a role for miR-302 in modulating BMP response

MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understo...

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Bibliographic Details
Published in:	Genes & development 2011-10, Vol.25 (20), p.2173-2186
Main Authors:	Lipchina, Inna, Elkabetz, Yechiel, Hafner, Markus, Sheridan, Robert, Mihailovic, Aleksandra, Tuschl, Thomas, Sander, Chris, Studer, Lorenz, Betel, Doron
Format:	Article
Language:	eng
Subjects:	Animals Bone morphogenetic proteins Bone Morphogenetic Proteins - metabolism Cell Differentiation Cell Line Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Gene Expression Profiling Gene Expression Regulation, Developmental Genome-Wide Association Study Humans Mice MicroRNAs - metabolism Protein Binding Research Paper RNA-Binding Proteins - metabolism Signal Transduction Transforming Growth Factor beta - metabolism
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Summary:	MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due to the lack of genome-wide strategies to identify their targets. Here, we performed comprehensive microRNA profiling in hESCs and in purified neural and mesenchymal derivatives. Using a combination of AGO cross-linking and microRNA perturbation experiments, together with computational prediction, we identified the targets of the miR-302/367 cluster, the most abundant microRNAs in hESCs. Functional studies identified novel roles of miR-302/367 in maintaining pluripotency and regulating hESC differentiation. We show that in addition to its role in TGF-β signaling, miR-302/367 promotes bone morphogenetic protein (BMP) signaling by targeting BMP inhibitors TOB2, DAZAP2, and SLAIN1. This study broadens our understanding of microRNA function in hESCs and is a valuable resource for future studies in this area.
ISSN:	0890-9369 1549-5477