Donor-derived spermatogenesis following stem cell transplantation in sterile <i>NANOS2</i> knockout males
Michela Ciccarelli, Mariana Ianello Giassetti, De‐Qiang Miao, Melissa J. Oatley, Colton Robbins, Blanca Lopez-Biladeau, Muhammad Waqas, Ahmed Tibary, Bruce Whitelaw, Simon Lillico, Chi‐Hun Park, Ki‐Eun Park, Bhanu P. Telugu, Zhiqiang Fan, Ying Liu, Misha Regouski, Irina A. Polejaeva, Jon M. Oatley
Abstract
Significance Transfer of sperm-producing stem cells isolated from a donor male into testes of a recipient male has important applications for preserving germplasm and as a conduit for widespread dissemination of desirable genetics in livestock production. A key aspect is surrogate males that lack endogenous germline but are otherwise physiologically normal. Here we demonstrate that male mice, pigs, and goats rendered genetically sterile by CRISPR-Cas9 editing of the NANOS2 gene support donor-derived spermatogenesis following allogeneic stem cell transplantation. In addition, we show that CRISPR-Cas9 editing of the NANOS2 gene in cattle leads to male germline ablation. These findings represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals.