Extracellular vesicles-mediated transfer of let-7b/7c promotes the proliferation of transition-state spermatogonia in neonatal mouse testis [scRNA-seq]

The self-renewal and differentiation of spermatogonial stem cells (SSCs) play essential roles in spermatogenesis. Extracellular vesicle (EV) is a universal strategy for intercellular communications in stem cell niches. However, the involvement of EVs in regulating the SSCs remains largely unknown. In this study, we have revealed the role of testis EVs isolated from postnatal day 7 (PND7) neonatal mouse testis in guiding spermatogonia into a transit-amplifying state with increased proliferation while retaining their differentiation potential. We profiled the repertoires of proteins and small RNAs by proteomic and small RNA transcriptomic analyses, respectively. We further showed that the EVs secreted by undifferentiated spermatogonia and the Sertoli cell lines, but not from more differentiated germ cell lines, conveyed let-7b/7c miRNA cargoes to spermatogonia, which mediates the effect of EVs on spermatognial transit amplification. Together, this study has deciphered an important intercellular communication within the spermatogonial niche mediated by let-7b/7c cargoes of EVs, providing a new insight into the regulation of SSCs and spermatogenesis.