Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males

Michela Ciccarelli, Mariana I. Giassetti, Deqiang Miao, Melissa J. Oatley, Colton Robbins, Blanca Lopez Biladeau, Muhamad Salman Waqas, Ahmed Tibary, Bruce Whitelaw, Simon Lillico, Chi-Hun Park, Ki-Eun Park, Bhanu Telugu, Zhiqiang Fan, Ying Liu, Misha Regouski, Irina A. Polejaeva, Jon M. Oatley

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)24195–24204
Number of pages10
JournalProceedings of the National Academy of Sciences
Volume117
Issue number39
Early online date14 Sep 2020
DOIs
Publication statusPublished - 29 Sep 2020

Keywords

  • NANOS2
  • Spermatological stem cell
  • Transplantation
  • Cattle
  • Pig
  • Goat
  • Mouse
  • Surrogate sires

Fingerprint Dive into the research topics of 'Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males'. Together they form a unique fingerprint.

Cite this