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 Mitchell, Meena Sukhwani, Ramesh C Tailor, Marvin L. Meistrich, Kyle E. Orwig, Gunapala Shetty, Amander T. Clark

Research output: Contribution to journalArticle

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

Sosa, E., Chen, D., Rojas, E. J., Hennebold, J. D., Peters, K. A., Wu, Z., ... Clark, A. T. (2018). Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche. Nature communications, 9(1), [5339]. https://doi.org/10.1038/s41467-018-07740-7

Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche. / Sosa, Enrique; Chen, Di; Rojas, Ernesto J.; Hennebold, Jon D.; Peters, Karen A.; Wu, Zhuang; Lam, Truong N.; Mitchell, Jennifer; 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, JD, Peters, KA, Wu, Z, Lam, TN, Mitchell, J, 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 D. ; Peters, Karen A. ; Wu, Zhuang ; Lam, Truong N. ; Mitchell, Jennifer ; 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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