Ngn1 inhibits astrogliogenesis through induction of miR-9 during neuronal fate specification.
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.
Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States.
Jing
J
Zhao
Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States.
Quan
Q
Lin
Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States.
Kevin J
KJ
Kim
Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States.
Faranak D
FD
Dardashti
Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States.
Jennifer
J
Kim
Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States.
Fei
F
He
Department of Psychiatry and Behavioral Sciences and Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, United States.
Yi
Y
Sun
D001253:Astrocytes / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D050822:Cytokine Receptor gp130 / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000037:antagonists & inhibitors; D035683:MicroRNAs / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D050822:Cytokine Receptor gp130; D053613:Janus Kinase 1; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C507841:Lifr protein, mouse; C551804:MIRN9 microRNA, mouse; C486336:Neurog1 protein, mouse; C507905:Jak1 protein, mouse
Jak; Stat; astrogliogenesis; developmental biology; microRNA-9; mouse; neurogenesis; neurogenin; neuroscience; stem cells