title: Secreted Ephrin Receptor A7 Promotes Somatic Cell Reprogramming by Inducing ERK Activity Reduction.
abstract: The role of secreted molecules in cellular reprogramming has been poorly understood. Here we identify a truncated form of ephrin receptor A7 (EPHA7) as a key regulator of reprogramming. Truncated EPHA7 is prominently upregulated and secreted during reprogramming. EPHA7 expression is directly regulated by OCT3/4. EphA7 knockdown results in marked reduction of reprogramming efficiency, and the addition of truncated EPHA7 is able to restore it. ERK activity is markedly reduced during reprogramming, and the secreted, truncated EPHA7 is responsible for ERK activity reduction. Remarkably, treatment of EphA7-knockdown MEFs with the ERK pathway inhibitor restores reprogramming efficiency. Analyses show that truncated EPHA7-induced ERK activity reduction plays an important role in the middle phase of reprogramming. Thus, our findings uncover the importance of secreted EPHA7-induced ERK activity reduction in reprogramming.
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Joonseong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan; JST, CREST, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: May
authors.initials: M
authors.lastname: Nakajima-Koyama
authors.affiliation: Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Sone
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan; RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Koga
authors.affiliation: RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; JST, CREST, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ebisuya
authors.affiliation: Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; JST, CREST, Chiyoda-ku, Tokyo 102-0075, 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; JST, CREST, Chiyoda-ku, Tokyo 102-0075, Japan. Electronic address: nishida@lif.kyoto-u.ac.jp.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008813:Mice, Inbred ICR; D036141:Receptor, EphA7 / Q000235:genetics / Q000378:metabolism*
chemical_list: D036141:Receptor, EphA7