학술논문

Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche.
Document Type
article
Source
Nature communications. 9(1)
Subject
Testis
Spermatocytes
Spermatogonia
Cells
Cultured
Animals
Macaca mulatta
Humans
Mice
Mice
Nude
Phosphopyruvate Hydratase
Neoplasm Proteins
Transplantation
Heterologous
Transplantation
Homologous
Spermatogenesis
Female
Male
Induced Pluripotent Stem Cells
Cells
Cultured
Nude
Transplantation
Heterologous
Homologous
Language
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.