RRC ID 57949
Author David BG, Fujita H, Yasuda K, Okamoto K, Panina Y, Ichinose J, Sato O, Horie M, Ichimura T, Okada Y, Watanabe TM.
Title Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells.
Journal Stem Cell Res
Abstract Pluripotency of mouse embryonic stem cells is regulated by transcription factor regulatory networks as well as mechanical stimuli sensed by the cells. It has been unclear how the mechanical strain applied to the plasma membrane is transferred to the nucleus in mouse embryonic stem cells (mESCs). We here investigated the machinery of the mechanotransduction based on the finding that spontaneous differentiation of mESCs was inhibited with the downregulation of ROCK2 in cells attached to soft substrates. On examining the effects of actin bindings to both focal adhesions and cell junctions in cells on soft substrates, co-localization of actin filaments and α-catenin, which links actin to E-cadherin, decreased after differentiation induction. Also, disrupting actin-nucleus mechanical link through dominant negative assay of Nesprins helps to sustain the pluripotency genes; thus, revealing that mechanical strain relayed by actin-Nesprin connection is required for the initiation of the differentiation process.
Volume 41
Pages 101614
Published 2019-12-1
DOI 10.1016/j.scr.2019.101614
PII S1873-5061(19)30244-2
PMID 31715427
MeSH Actin Cytoskeleton / pathology* Animals Cadherins / metabolism Cell Differentiation* Cell Line Cell Nucleus / metabolism* Gene Expression Regulation, Enzymologic Mice Mouse Embryonic Stem Cells / cytology Mouse Embryonic Stem Cells / metabolism* alpha Catenin / metabolism rho-Associated Kinases / biosynthesis
IF 4.495
Times Cited 1
Resource
Human and Animal Cells E14tg2a(AES0135)