Tcf21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration

Testicular development and function relies on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity decline in aging and disease. Whether the adult testis maintains a reserve progenitor population with repair or regenerative capacity remains uncertain. Here, we characterized a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that Tcf21+ cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as reserve somatic progenitors following injury. In vitro, Tcf21+ 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 leveraged in development of future therapies for hypoandrogenism and/or infertility. HighlightsO_LIMultipotent Tcf21+ MPs can differentiate into somatic testis cell types C_LIO_LITcf21+ cells contribute to testis and ovary somatic cells during gonadal development C_LIO_LITcf21+ cells replenish somatic cells of the aging testis and in response to tissue injury C_LIO_LITestis Tcf21 cells resemble resident fibroblast populations in multiple organs C_LI