Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 39, Pages 24195-24204Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2010102117
Keywords
NANOS2; spermatogonial stem cell; transplantation; surrogate sires; livestock
Categories
Funding
- US Department of Agriculture (USDA)-National Institute of Food and Agriculture (NIFA) [2017-05436]
- USDA-NIFA [2018-06478]
- Washington State University
- Utah State University
- Genus plc
- BBSRC [BB/M018342/1, BBS/E/D/10002071, BB/N015339/1, BBS/E/D/20221658, BBS/E/D/20221656, BB/M028313/1, BB/L007371/1] Funding Source: UKRI
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Spermatogonial stem cell transplantation (SSCT) is an experimental technique for transfer of germline between donor and recipient males that could be used as a tool for biomedical research, preservation of endangered species, and dissemination of desirable genetics in food animal populations. To fully realize these potentials, recipient males must be devoid of endogenous germline but possess normal testicular architecture and somatic cell function capable of supporting allogeneic donor stem cell engraftment and regeneration of spermatogenesis. Here we show that male mice, pigs, goats, and cattle harboring knockout alleles of the NANOS2 gene generated by CRISPR-Cas9 editing have testes that are germline ablated but otherwise structurally normal. In adult pigs and goats, SSCT with allogeneic donor stem cells led to sustained donor-derived spermatogenesis. With prepubertal mice, allogeneic SSCT resulted in attainment of natural fertility. Collectively, these advancements represent a major step toward realizing the enormous potential of surrogate sires as a tool for dissemination and regeneration of germplasm in all mammalian species.
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