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13 November 2019 Induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeys
Yoshitake Sakai, Tomonori Nakamura, Ikuhiro Okamoto, Sayuri Gyobu-Motani, Hiroshi Ohta, Yukihiro Yabuta, Tomoyuki Tsukiyama, Chiduru Iwatani, Hideaki Tsuchiya, Masatsugu Ema, Asuka Morizane, Jun Takahashi, Takuya Yamamoto, Mitinori Saitou
Author Affiliations +
Abstract

In vitro reconstitution of germ-cell development from pluripotent stem cells (PSCs) has created key opportunities to explore the fundamental mechanisms underlying germ-cell development, particularly in mice and humans. Importantly, such investigations have clarified critical species differences in the mechanisms regulating mouse and human germ-cell development, highlighting the necessity of establishing an in vitro germ-cell development system in other mammals, such as non-human primates. Here, we show that multiple lines of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in cynomolgus monkeys (Macaca fascicularis; cy) can be maintained stably in an undifferentiated state under a defined condition with an inhibitor for WNT signaling, and such PSCs are induced efficiently into primordial germ cell-like cells (PGCLCs) bearing a transcriptome similar to early cyPGCs. Interestingly, the induction kinetics of cyPGCLCs from cyPSCs is faster than that of human (h) PGCLCs from hPSCs, and while the transcriptome dynamics during cyPGCLC induction is relatively similar to that during hPGCLC induction, it is substantially divergent from that during mouse (m) PGCLC induction. Our findings delineate common as well as species-specific traits for PGC specification, creating a foundation for parallel investigations into the mechanism for germ-cell development in mice, monkeys, and humans.

Summary Sentence

Pluripotent stem cells in cynomolgus monkeys are induced into primordial germ cell-like cells with species-specific kinetics and transcriptome dynamics.

© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Yoshitake Sakai, Tomonori Nakamura, Ikuhiro Okamoto, Sayuri Gyobu-Motani, Hiroshi Ohta, Yukihiro Yabuta, Tomoyuki Tsukiyama, Chiduru Iwatani, Hideaki Tsuchiya, Masatsugu Ema, Asuka Morizane, Jun Takahashi, Takuya Yamamoto, and Mitinori Saitou "Induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeys," Biology of Reproduction 102(3), 620-638, (13 November 2019). https://doi.org/10.1093/biolre/ioz205
Received: 11 July 2019; Accepted: 19 October 2019; Published: 13 November 2019
KEYWORDS
cynomolgus monkeys
evolution
gene expression
pluripotent stem cells
primordial germ cells
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