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 and Amander T. Clark ()
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Enrique Sosa: University of California, Los Angeles
Di Chen: University of California, Los Angeles
Ernesto J. Rojas: University of California, Los Angeles
Jon D. Hennebold: Oregon National Primate Research Center
Karen A. Peters: University of Pittsburgh School of Medicine
Zhuang Wu: University of Texas MD Anderson Cancer Center
Truong N. Lam: University of Texas MD Anderson Cancer Center
Jennifer M. Mitchell: University of Texas MD Anderson Cancer Center
Meena Sukhwani: University of Pittsburgh School of Medicine
Ramesh C. Tailor: University of Texas MD Anderson Cancer Center
Marvin L. Meistrich: University of Texas MD Anderson Cancer Center
Kyle E. Orwig: University of Pittsburgh School of Medicine
Gunapala Shetty: University of Texas MD Anderson Cancer Center
Amander T. Clark: University of California, Los Angeles

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07740-7

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