Ngn1 inhibits astrogliogenesis through induction of miR-9 during neuronal fate specification

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Abstract

It has been postulated that a proneural factor, neurogenin 1 (Ngn1), simultaneously activates the neurogenic program and inhibits the alternative astrogliogenic program when specifying the neuronal fate. While Ngn1 substantially suppresses the activation of the astrogliogenic Jak-Stat pathway, the underlying molecular mechanism was unknown. Here, by employing in vivo and in vitro approaches, we report that Ngn1 binds to the promoter of a brain-enriched microRNA, miR-9, and activates its expression during neurogenesis. Subsequently, our in vitro study showed that miR-9 directly targets mRNAs of Lifr-beta, Il6st (gp130), and Jak1 to down-regulate these critical upstream components of the Jak-Stat pathway, achieving inhibition of Stat phosphorylation and consequently, suppression of astrogliogenesis. This study revealed Ngn1 modulated non-coding RNA epigenetic regulation during cell fate specifications.

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Jing Zhao

Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Quan Lin

Stem Cell Translational Research Center, Tongji University School of Medicine, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Kevin J Kim

Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Faranak D Dardashti

Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Jennifer Kim

Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Yi Sun

Stem Cell Translational Research Center, Tongji University School of Medicine, Shanghai, China

For correspondence
ysun@mednet.ucla.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and Chancellor's Animal Research Committee (ARC) protocol #2002001 of UCLA.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.