title: A developmental coordinate of pluripotency among mice, monkeys and humans.
abstract: The epiblast (EPI) is the origin of all somatic and germ cells in mammals, and of pluripotent stem cells in vitro. To explore the ontogeny of human and primate pluripotency, here we perform comprehensive single-cell RNA sequencing for pre- and post-implantation EPI development in cynomolgus monkeys (Macaca fascicularis). We show that after specification in the blastocysts, EPI from cynomolgus monkeys (cyEPI) undergoes major transcriptome changes on implantation. Thereafter, while generating gastrulating cells, cyEPI stably maintains its transcriptome over a week, retains a unique set of pluripotency genes and acquires properties for 'neuron differentiation'. Human and monkey pluripotent stem cells show the highest similarity to post-implantation late cyEPI, which, despite co-existing with gastrulating cells, bears characteristics of pre-gastrulating mouse EPI and epiblast-like cells in vitro. These findings not only reveal the divergence and coherence of EPI development, but also identify a developmental coordinate of the spectrum of pluripotency among key species, providing a basis for better regulation of human pluripotency in vitro.
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Okamoto
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yabuta
authors.affiliation: Research Center for Animal Life Science, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Chizuru
authors.initials: C
authors.lastname: Iwatani
authors.affiliation: Research Center for Animal Life Science, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Research Center for Animal Life Science, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Seita
authors.affiliation: Research Center for Animal Life Science, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.|Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan.|AMED-CREST, AMED, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.|Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Mitinori
authors.initials: M
authors.lastname: Saitou
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006801:Humans; D008252:Macaca fascicularis / Q000196:embryology* / Q000235:genetics; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D013045:Species Specificity; D059467:Transcriptome