Generation of spermatogonia from human and non-human primate pluripotent stem cells
5 affiliations
- 1Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, USA. Electronic address: [email protected]
- 2Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, USA
- 3Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, USA; Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube, Japan
- 4Regensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany; National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
- 5National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
Abstract
Failures in germline development drive male infertility, but the lack of model systems that recapitulate human spermatogenesis hampers therapeutic development. Here, we develop a system to differentiate human-induced pluripotent stem cells (iPSCs) into primordial germ cell-like cells that self-organize with mouse fetal testicular cells into seminiferous tubule-like structures within a xenogeneic reconstituted testis (xrTestis). Subsequent transplantation of xrTestes into immunodeficient mice results in efficient generation of male germ cells up to meiotic onset, including spermatogonia with evidence of prepachytene PIWI-interacting RNA (piRNA) biogenesis, as well as differentiating spermatogonia and rare preleptotene spermatocytes exhibiting transcriptomic and phenotypic similarities to their in vivo counterparts. As future clinical applications will require testing in non-human primates, we apply a similar strategy to differentiate rhesus iPSCs through fetal germ cell stages into spermatogonia and differentiating spermatogonia. Together, these platforms provide a foundation for studying primate germ cell lineages and represent a step toward in vitro gametogenesis.
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BibTeX
@article{whelan2026generation,
title = {{Generation of spermatogonia from human and non-human primate pluripotent stem cells}},
author = {Eoin Christopher Whelan and Mingyue Guo and Ryo Yokomizo and Yasunari Seita and Young Sun Hwang and Yuichiro Shirafuta and Nicolae Adrian Leu and Keren Cheng and Franziska Ahrend and Astrid D. Haase and Kotaro Sasaki},
journal = {Cell stem cell},
year = {2026},
month = jul,
doi = {10.1016/j.stem.2026.06.001},
url = {https://doi.org/10.1016/j.stem.2026.06.001},
note = {CC BY},
}
RIS
TY - JOUR
TI - Generation of spermatogonia from human and non-human primate pluripotent stem cells
AU - Eoin Christopher Whelan
AU - Mingyue Guo
AU - Ryo Yokomizo
AU - Yasunari Seita
AU - Young Sun Hwang
AU - Yuichiro Shirafuta
AU - Nicolae Adrian Leu
AU - Keren Cheng
AU - Franziska Ahrend
AU - Astrid D. Haase
AU - Kotaro Sasaki
PY - 2026
DA - 2026/07/10
JO - Cell stem cell
DO - 10.1016/j.stem.2026.06.001
UR - https://doi.org/10.1016/j.stem.2026.06.001
AB - Failures in germline development drive male infertility, but the lack of model systems that recapitulate human spermatogenesis hampers therapeutic development. Here, we develop a system to differentiate human-induced pluripotent stem cells (iPSCs) into primordial germ cell-like cells that self-organize with mouse fetal testicular cells into seminiferous tubule-like structures within a xenogeneic reconstituted testis (xrTestis). Subsequent transplantation of xrTestes into immunodeficient mice results in efficient generation of male germ cells up to meiotic onset, including spermatogonia with evidence of prepachytene PIWI-interacting RNA (piRNA) biogenesis, as well as differentiating spermatogonia and rare preleptotene spermatocytes exhibiting transcriptomic and phenotypic similarities to their in vivo counterparts. As future clinical applications will require testing in non-human primates, we apply a similar strategy to differentiate rhesus iPSCs through fetal germ cell stages into spermatogonia and differentiating spermatogonia. Together, these platforms provide a foundation for studying primate germ cell lineages and represent a step toward in vitro gametogenesis.
SN - 1875-9777
SN - 1934-5909
ER -