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LincU Preserves Naïve Pluripotency by Restricting ERK Activity in Embryonic Stem Cells.

Abstract：

:Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit a primed-like pluripotent state and potentiate the transition from the naïve state to the primed state, whereas ectopic LincU expression maintains mESCs in the naïve state. Mechanistically, we demonstrate that LincU binds and stabilizes the DUSP9 protein, an ERK-specific phosphatase, and then constitutively inhibits the ERK1/2 signaling pathway, which critically contributes to maintenance of the naïve state. Importantly, we reveal the functional role of LincU to be evolutionarily conserved in human. Therefore, our findings unveil LincU as a conserved lncRNA that intrinsically restricts MAPK/ERK activity and maintains the naïve state of ESCs.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Jiapaer Z,Li G,Ye D,Bai M,Li J,Guo X,Du Y,Su D,Jia W,Chen W,Wang G,Yu Y,Zhu F,Wan X,Kang J

doi

10.1016/j.stemcr.2018.06.010

subject

Has Abstract

pub_date

2018-08-14 00:00:00

pages

395-409

issue

2

issn

2213-6711

pii

S2213-6711(18)30273-X

journal_volume

11

pub_type

杂志文章

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