Abstract
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 TCF21lin 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, TCF21lin 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.
Highlights
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
In contrast with these cell types, Tcf21+ cells did not express any of their terminally differentiated markers (Fig. 1C). This population was uniquely demarcated by the expression of Tcf[21], Pdgfra, CoupTFII, and mesenchymal progenitor cell (MP) markers including Sca[1] (Fig. 1C, Supplementary Data 1), Arx, and Vim[13]
As the SCA1+/TCF21lin cells were labeled as a population, the results described above could not distinguish between two scenarios: (1) each TCF21lin/SCA1+ cell is a multipotent progenitor, capable of adopting any of multiple fates, or (2) these cells are heterogeneous, comprised of multiple subtypes of progenitors that each have been cryptically committed to differentiate into a different somatic lineage
Summary
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. Others have shown that testicular endothelial cells[14] as well as lymphatic endothelial cells[15] support human and mouse spermatogonial stem cell survival and expansion, and can modulate spermatogonial cell homeostasis and regeneration[15] These studies underscore the importance of defining the interstitial cell composition and function. Without single-cell RNA-seq analysis it remains difficult to tease apart whether these markers are observed in a single homogenous population of Leydig stem cells or if these cells are a heterogenous pool of progenitors It is unclear if a common somatic progenitor could give rise to additional cell types other than Leydig, and what the role of such stem/progenitors would be in the normal adult testis
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