Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche

Enrique Sosa, Di Chen, Ernesto J. Rojas, Jon D. Hennebold, Karen A. Peters, Zhuang Wu, Truong N. Lam, Jennifer M. Mitchell, Meena Sukhwani, Ramesh C. Tailor, Marvin L. Meistrich, Kyle E. Orwig, Gunapala Shetty, Amander T. Clark

    Research output: Contribution to journalArticlepeer-review

    5 Scopus citations

    Abstract

    A major challenge in stem cell differentiation is the availability of bioassays to prove cell types generated in vitro are equivalent to cells in vivo. In the mouse, differentiation of primordial germ cell-like cells (PGCLCs) from pluripotent cells was validated by transplantation, leading to the generation of spermatogenesis and to the birth of offspring. Here we report the use of xenotransplantation (monkey to mouse) and homologous transplantation (monkey to monkey) to validate our in vitro protocol for differentiating male rhesus (r) macaque PGCLCs (rPGCLCs) from induced pluripotent stem cells (riPSCs). Specifically, transplantation of aggregates containing rPGCLCs into mouse and nonhuman primate testicles overcomes a major bottleneck in rPGCLC differentiation. These findings suggest that immature rPGCLCs once transplanted into an adult gonadal niche commit to differentiate towards late rPGCs that initiate epigenetic reprogramming but do not complete the conversion into ENO2-positive spermatogonia.

    Original languageEnglish (US)
    Article number5339
    JournalNature communications
    Volume9
    Issue number1
    DOIs
    StatePublished - Dec 1 2018

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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