Pluripotency factor NANOG promotes germ cell maintenance in vitro without triggering dedifferentiation of spermatogonial stem cells

Theriogenology. 2020 May:148:68-75. doi: 10.1016/j.theriogenology.2020.02.028. Epub 2020 Feb 21.

Abstract

Spermatogonial stem cells (SSCs) are defined as the tissue-specific stem cells in the testes that produce sperm and support life-long spermatogenesis. A culture microenvironment could convert mouse SSCs from unipotent to pluripotent states; however, the underlying mechanism is unclear. NANOG has been considered the decisive transcriptional factor for pluripotency transition of stem cells, but NANOG is not expressed in SSCs. Here, we investigated whether NANOG overexpression could result in SSCs being converted into a pluripotent state. We found that rare NANOG-positive cells could be detected in spermatogonia, pachytene spermatocytes, and even round spermatids in mouse testes, and that the induction of NANOG could promote the proliferation of cultured SSCs in vitro and partially compensate for the role of the growth factor GDNF. In vivo allogeneic transplantation of NANOG-overexpressing germ cells did not yield any teratoma-like tissues, but regenerated normal colonies of spermatogenesis in the testes of recipient mice. Collectively, our data showed that overexpression of the pluripotency factor NANOG along did not dedifferentiate testis germline stem cells into a pluripotent state, suggesting that other genetic or epigenetic factors are involved in SSC reprogramming.

Keywords: NANOG; Pluripotency; Spermatogonial stem cell; Testis; Transplantation.

MeSH terms

  • Animals
  • Cell Dedifferentiation / physiology*
  • Gene Expression Regulation
  • Male
  • Mice
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Spermatogenesis
  • Spermatogonia / physiology*
  • Stem Cell Transplantation
  • Stem Cells / metabolism*
  • Testis / metabolism

Substances

  • Nanog Homeobox Protein
  • Nanog protein, mouse