title: Integrative Analysis of the Acquisition of Pluripotency in PGCs Reveals the Mutually Exclusive Roles of Blimp-1 and AKT Signaling.
abstract: Primordial germ cells (PGCs) are lineage-restricted unipotent cells that can dedifferentiate into pluripotent embryonic germ cells (EGCs). Here we performed whole-transcriptome analysis during the conversion of PGCs into EGCs, a process by which cells acquire pluripotency. To examine the molecular mechanism underlying this conversion, we focused on Blimp-1 and Akt, which are involved in PGC specification and dedifferentiation, respectively. Blimp-1 overexpression in embryonic stem cells suppressed the expression of downstream targets of the pluripotency network. Conversely, Blimp-1 deletion in PGCs accelerated their dedifferentiation into pluripotent EGCs, illustrating that Blimp-1 is a pluripotency gatekeeper protein in PGCs. AKT signaling showed a synergistic effect with basic fibroblast growth factor plus 2i+A83 treatment on EGC formation. AKT played a major role in suppressing genes regulated by MBD3. From these results, we defined the distinct functions of Blimp-1 and Akt and provided mechanistic insights into the acquisition of pluripotency in PGCs.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan; Department of Stem Cell Biology and Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: gonag@hgs.med.kyushu-u.ac.jp.
authors.forename: Go
authors.initials: G
authors.lastname: Nagamatsu
authors.affiliation: Data Science Lab, OPT, Tokyo 102-0081, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582, Japan; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Keiyo
authors.initials: K
authors.lastname: Takubo
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582, Japan; Cancer Science Institute (CSI), National University of Singapore (NUS), 14 Medical Drive, Singapore 117599, Singapore; International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, 860-0811, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D000066473:Embryonic Germ Cells; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology / Q000254:growth & development; D051379:Mice; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D039904:Pluripotent Stem Cells; D000074462:Positive Regulatory Domain I-Binding Factor 1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051058:Oncogene Protein v-akt