title: Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem 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.
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Ashida
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.|AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
authors.forename: May
authors.initials: M
authors.lastname: Nakajima-Koyama
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hirota
authors.affiliation: AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.|Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.|Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.|AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
mesh_terms: D028341:Activins / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases