RRC ID 52057
Author Ashida Y, Nakajima-Koyama M, Hirota A, Yamamoto T, Nishida E.
Title Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells.
Journal Genes Cells
Abstract The Activin/Nodal/TGF-β signaling pathway plays a major role in maintaining mouse epiblast stem cells (EpiSCs). The EpiSC-maintaining medium, which contains Activin A and bFGF, induces differentiation of mouse embryonic stem cells (ESCs) to EpiSCs. Here, we show that Activin A also has an ability to efficiently propagate ESCs without differentiation to EpiSCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors. Genomewide analysis showed that the gene expression profile of ESCs cultured in Activin+PD resembles that of ESCs cultured in 2i. ESCs cultured in Activin+PD also showed features common to the naive pluripotency of ESCs, including the preferential usage of the Oct4 distal enhancer and the self-renewal response to Wnt pathway activation. Our finding shows a role of Activin/Nodal/TGF-β signaling in stabilizing self-renewal gene regulatory networks in ESCs.
Volume 22(2)
Pages 189-202
Published 2017-2-1
DOI 10.1111/gtc.12467
PMID 28097777
MeSH Activins / chemistry Activins / pharmacology* Animals Cell Differentiation / physiology Cell Proliferation / physiology Cells, Cultured Germ Layers / cytology Germ Layers / metabolism HEK293 Cells Humans MAP Kinase Signaling System / drug effects* MAP Kinase Signaling System / physiology Mice Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases / metabolism Mouse Embryonic Stem Cells / cytology Mouse Embryonic Stem Cells / drug effects* Mouse Embryonic Stem Cells / metabolism* Pluripotent Stem Cells / cytology Pluripotent Stem Cells / drug effects Pluripotent Stem Cells / metabolism Transcription Factors / metabolism Transforming Growth Factor beta / metabolism Wnt Signaling Pathway
IF 1.655
Times Cited 5
Human and Animal Cells E14tg2a(AES0135)