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

Enrique Sosa, Di Chen, Ernesto J. Rojas, Jon 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 journalArticle

    2 Citations (Scopus)

    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

    Fingerprint

    primates
    transplantation
    Cell Transplantation
    Stem cells
    monkeys
    Germ Cells
    Primates
    Cells
    mice
    Macaca
    Bioassay
    stem cells
    Haplorhini
    cells
    spermatogenesis
    Availability
    bioassay
    Transplantation
    Induced Pluripotent Stem Cells
    Heterologous Transplantation

    ASJC Scopus subject areas

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

    Cite this

    Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche. / Sosa, Enrique; Chen, Di; Rojas, Ernesto J.; Hennebold, Jon; Peters, Karen A.; Wu, Zhuang; Lam, Truong N.; Mitchell, Jennifer M.; Sukhwani, Meena; Tailor, Ramesh C.; Meistrich, Marvin L.; Orwig, Kyle E.; Shetty, Gunapala; Clark, Amander T.

    In: Nature Communications, Vol. 9, No. 1, 5339, 01.12.2018.

    Research output: Contribution to journalArticle

    Sosa, E, Chen, D, Rojas, EJ, Hennebold, J, Peters, KA, Wu, Z, Lam, TN, Mitchell, JM, Sukhwani, M, Tailor, RC, Meistrich, ML, Orwig, KE, Shetty, G & Clark, AT 2018, 'Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche', Nature Communications, vol. 9, no. 1, 5339. https://doi.org/10.1038/s41467-018-07740-7
    Sosa, Enrique ; Chen, Di ; Rojas, Ernesto J. ; Hennebold, Jon ; Peters, Karen A. ; Wu, Zhuang ; Lam, Truong N. ; Mitchell, Jennifer M. ; Sukhwani, Meena ; Tailor, Ramesh C. ; Meistrich, Marvin L. ; Orwig, Kyle E. ; Shetty, Gunapala ; Clark, Amander T. / Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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