title: Epiblast stem cell-based system reveals reprogramming synergy of germline factors.
abstract: Epigenetic reprogramming in early germ cells is critical toward the establishment of totipotency, but investigations of the germline events are intractable. An objective cell culture-based system could provide mechanistic insight on how the key determinants of primordial germ cells (PGCs), including Prdm14, induce reprogramming in germ cells to an epigenetic ground state. Here we show a Prdm14-Klf2 synergistic effect that can accelerate and enhance reversion of mouse epiblast stem cells (epiSCs) to a naive pluripotent state, including X reactivation and DNA demethylation. Notably, Prdm14 alone has little effect on epiSC reversion, but it enhances the competence for reprogramming and potentially PGC specification. Reprogramming of epiSCs by the combinatorial effect of Prdm14-Klf2 involves key epigenetic changes, which might have an analogous role in PGCs. Our study provides a paradigm toward a systematic analysis of how other key genes contribute to complex and dynamic events of reprogramming in the germline.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, UK.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gillich
authors.forename: Siqin
authors.initials: S
authors.lastname: Bao
authors.forename: Nils
authors.initials: N
authors.lastname: Grabole
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Matthew W B
authors.initials: MW
authors.lastname: Trotter
authors.forename: Vincent
authors.initials: V
authors.lastname: Pasque
authors.forename: Erna
authors.initials: E
authors.lastname: Magnúsdóttir
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D005854:Germ Cells / Q000166:cytology; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C096161:KLF2 protein, human; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; C524724:PRDM14 protein, human; C531066:Prdm14 protein, mouse; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors