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microRNA‐17‐92 cluster is a direct Nanog target and controls neural stem cell through Trp53inp1
Author(s) -
Garg Neha,
Po Agnese,
Miele Evelina,
Campese Antonio Francesco,
Begalli Federica,
Silvano Marianna,
Infante Paola,
Capalbo Carlo,
De Smaele Enrico,
Canettieri Gianluca,
Di Marcotullio Lucia,
Screpanti Isabella,
Ferretti Elisabetta,
Gulino Alberto
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.214
Subject(s) - homeobox protein nanog , biology , microrna , nanog homeobox protein , psychological repression , neural stem cell , transcription factor , embryonic stem cell , rex1 , stem cell , microbiology and biotechnology , genetics , sox2 , induced pluripotent stem cell , gene expression , gene
The transcription factor Nanog plays a critical role in the self‐renewal of embryonic stem cells as well as in neural stem cells (NSCs). microRNAs (miRNAs) are also involved in stemness regulation. However, the miRNA network downstream of Nanog is still poorly understood. High‐throughput screening of miRNA expression profiles in response to modulated levels of Nanog in postnatal NSCs identifies miR‐17‐92 cluster as a direct target of Nanog. Nanog controls miR‐17‐92 cluster by binding to the upstream regulatory region and maintaining high levels of transcription in NSCs, whereas Nanog/promoter association and cluster miRNAs expression are lost alongside differentiation. The two miR‐17 family members of miR‐17‐92 cluster, namely miR‐17 and miR‐20a, target Trp53inp1, a downstream component of p53 pathway. To support a functional role, the presence of miR‐17/20a or the loss of Trp53inp1 is required for the Nanog‐induced enhancement of self‐renewal of NSCs. We unveil an arm of the Nanog/p53 pathway, which regulates stemness in postnatal NSCs, wherein Nanog counteracts p53 signals through miR‐17/20a‐mediated repression of Trp53inp1.