FOXP4 promotes proliferation of human spermatogonial stem cells

Continuous self-renewal and differentiation of spermatogonial stem cells (SSCs) is vital for maintenance of adult spermatogenesis. Although several spermatogonial stem cell regulators have been extensively investigated in rodents, regulatory mechanisms of human SSC self-renewal and differentiation have not been fully established. We analyzed single-cell sequencing data from the human testis and found that forkhead box P4 (FOXP4) expression gradually increased with development of SSCs. Further analysis of its expression patterns in human testicular tissues revealed that FOXP4 specifically marks a subset of spermatogonia with stem cell potential. Conditional inactivation of FOXP4 in human SSC lines suppressed SSC proliferation and significantly activated apoptosis. FOXP4 expressions were markedly suppressed in tissues with dysregulated spermatogenesis. These findings imply that FOXP4 is involved in human SSC proliferation, which will help elucidate on the mechanisms controlling the fate decisions in human SSCs.

Automated summary

FOXP4 expression gradually increased during the development of human SSCs. It specifically marks a subset of spermatogonia with stem cell potential. Inactivation of FOXP4 suppressed SSC proliferation and activated apoptosis. These findings suggest the involvement of FOXP4 in human SSC proliferation and provide insights into the mechanisms controlling fate decisions in human SSCs.