4.8 Article

TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41467-021-24130-8

Keywords

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Funding

  1. National Institute of Health (NIH) [1R21HD090371-01A1, 1DP2HD091949-01, R01 HD092084, F30HD097961, F31HD100124, 5T32HD079342, 5T32GM007863]
  2. NSF [1256260 DGE]
  3. Rackham Predoctoral Fellowship
  4. Michigan Institute for Data Science (MIDAS) grant for Health Sciences Challenge Award
  5. Open Philanthropy Grant [2019-199327 (5384)]
  6. [T32GM007315]
  7. [T32HD007505]

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Researchers have identified a population of testis interstitial cells expressing the transcription factor Tcf21, which help maintain adult testis homeostasis and potentially act as reserve somatic progenitors following aging and injury. These cells exhibit multipotent mesenchymal progenitor characteristics and can differentiate into various somatic cell types.
Testicular development and function rely on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity declines in aging and disease. Whether the adult testis maintains a reserve progenitor population remains uncertain. Here, we characterize a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that TCF21(lin) cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury. In vitro, TCF21(lin) cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, TCF21(+) cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be potentially leveraged in development of future therapies for hypoandrogenism and/or infertility. Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.

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