| Literature DB >> 33637711 |
Toshihiro Kobayashi1,2, Teppei Goto3, Mami Oikawa3, Makoto Sanbo3, Fumika Yoshida3, Reiko Terada3, Naoko Niizeki3, Naoyo Kajitani4, Kanako Kazuki4, Yasuhiro Kazuki4,5, Shinichi Hochi6, Hiromitsu Nakauchi7,8, M Azim Surani9,10, Masumi Hirabayashi11,12.
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.Entities:
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Year: 2021 PMID： 33637711 PMCID： PMC7910474 DOI： 10.1038/s41467-021-21557-x
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919