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

Autor: Kobayashi T; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan. tkoba@nips.ac.jp.; The Graduate University of Advanced Studies, Okazaki, Aichi, Japan. tkoba@nips.ac.jp., Goto T; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan., Oikawa M; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan., Sanbo M; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan., Yoshida F; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan., Terada R; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan., Niizeki N; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan., Kajitani N; Chromosome Engineering Research Center, Tottori University, Yonago, Tottori, Japan., Kazuki K; Chromosome Engineering Research Center, Tottori University, Yonago, Tottori, Japan., Kazuki Y; Chromosome Engineering Research Center, Tottori University, Yonago, Tottori, Japan.; Division of Genome and Cellular Functions, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan., Hochi S; Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano, Japan., Nakauchi H; Division of Stem Cell Therapy, Distinguished Professor Unit, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.; Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Surani MA; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK., Hirabayashi M; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan. mhirarin@nips.ac.jp.; The Graduate University of Advanced Studies, Okazaki, Aichi, Japan. mhirarin@nips.ac.jp.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Feb 26; Vol. 12 (1), pp. 1328. Date of Electronic Publication: 2021 Feb 26.
DOI: 10.1038/s41467-021-21557-x
Abstrakt: 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.
Databáze: MEDLINE
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