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Blastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats

Author

Listed:
  • Toshihiro Kobayashi

    (National Institute for Physiological Sciences
    The Graduate University of Advanced Studies)

  • Teppei Goto

    (National Institute for Physiological Sciences)

  • Mami Oikawa

    (National Institute for Physiological Sciences)

  • Makoto Sanbo

    (National Institute for Physiological Sciences)

  • Fumika Yoshida

    (National Institute for Physiological Sciences)

  • Reiko Terada

    (National Institute for Physiological Sciences)

  • Naoko Niizeki

    (National Institute for Physiological Sciences)

  • Naoyo Kajitani

    (Tottori University)

  • Kanako Kazuki

    (Tottori University)

  • Yasuhiro Kazuki

    (Tottori University
    Tottori University)

  • Shinichi Hochi

    (Shinshu University)

  • Hiromitsu Nakauchi

    (The University of Tokyo
    Stanford University School of Medicine)

  • M. Azim Surani

    (University of Cambridge
    University of Cambridge)

  • Masumi Hirabayashi

    (National Institute for Physiological Sciences
    The Graduate University of Advanced Studies)

Abstract

Murine animal models from genetically modified pluripotent stem cells (PSCs) are essential for functional genomics and biomedical research, which require germline transmission for the establishment of colonies. However, the quality of PSCs, and donor-host cell competition in chimeras often present strong barriers for germline transmission. Here, we report efficient germline transmission of recalcitrant PSCs via blastocyst complementation, a method to compensate for missing tissues or organs in genetically modified animals via blastocyst injection of PSCs. We show that blastocysts from germline-deficient Prdm14 knockout rats provide a niche for the development of gametes originating entirely from the donor PSCs without any detriment to somatic development. We demonstrate the potential of this approach by creating PSC-derived Pax2/Pax8 double mutant anephric rats, and rescuing germline transmission of a PSC carrying a mouse artificial chromosome. Furthermore, we generate mouse PSC-derived functional spermatids in rats, which provides a proof-of-principle for the generation of xenogenic gametes in vivo. We believe this approach will become a useful system for generating PSC-derived germ cells in the future.

Suggested Citation

  • Toshihiro Kobayashi & Teppei Goto & Mami Oikawa & Makoto Sanbo & Fumika Yoshida & Reiko Terada & Naoko Niizeki & Naoyo Kajitani & Kanako Kazuki & Yasuhiro Kazuki & Shinichi Hochi & Hiromitsu Nakauchi , 2021. "Blastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21557-x
    DOI: 10.1038/s41467-021-21557-x
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    Cited by:

    1. Hisato Nagano & Naoaki Mizuno & Hideyuki Sato & Eiji Mizutani & Ayaka Yanagida & Mayuko Kano & Mariko Kasai & Hiromi Yamamoto & Motoo Watanabe & Fabian Suchy & Hideki Masaki & Hiromitsu Nakauchi, 2024. "Skin graft with dermis and appendages generated in vivo by cell competition," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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