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

Authors: Lipchina, I.; Elkabetz, Y.; Hafner, M.; Sheridan, R.; Mihailovic, A.; Tuschl, T.; Sander, C.; Studer, L.; Betel, D.
Article Title: Genome-wide identification of microRNA targets in human ES cells reveals a role for miR-302 in modulating BMP response
Abstract: 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-b 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. © 2011 by Cold Spring Harbor Laboratory Press.
Keywords: signal transduction; controlled study; unclassified drug; human cell; nonhuman; animal cell; mouse; animals; mice; microrna; gene expression profiling; computational biology; bone morphogenetic protein; transforming growth factor beta; embryonic stem cell; cell line; protein binding; genetic association; genome-wide association study; cell differentiation; gene expression regulation, developmental; rna-binding proteins; immunoprecipitation; stem cells; embryonic stem cells; target cell; pluripotent stem cell; micrornas; protein cross linking; mesenchyme; argonaute 2 protein; bone morphogenetic proteins; mirna; mir-302; stem cell differentiatio; microrna 302
Journal Title: Genes and Development
Volume: 25
Issue: 20
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2011-10-15
Start Page: 2173
End Page: 2186
Language: English
DOI: 10.1101/gad.17221311
PROVIDER: scopus
PMCID: PMC3205587
PUBMED: 22012620
Notes: --- - "Export Date: 9 December 2011" - "CODEN: GEDEE" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Lorenz Studer
    190 Studer
  2. Doron Betel
    10 Betel
  3. Chris Sander
    210 Sander