Dissecting the spermatogonial stem cell niche using spatial transcriptomics

Spermatogonial stem cells (SSCs) in the testis support the lifelong production of sperm. SSCs reside within specialized microenvironments called niches,which are essential for SSC self-renewal and differentiation. However, our understanding of the molecular and cellular interactions between SSCs and niches remains incomplete. Here, we combine spatial transcriptomics, computational analyses, and functional assays to systematically dissect the molecular, cellular, and spatial composition of SSC niches. This allows us to spatially map the ligand-receptor (LR) interaction landscape in both mouse and human testes. Our data demonstrate that pleiotrophin regulates mouse SSC functions through syndecan receptors. We also identify ephrin-A1 as a potential niche factor that influences human SSC functions. Furthermore, we show that the spatial re-distribution of inflammation-related LR interactions underlies diabetes-induced testicular injury. Together, our study demonstrates a systems approach to dissect the complex organization of the stem cell microenvironment in health and disease.

Automated summary

In this study, the molecular, cellular, and spatial composition of SSC niches was systematically dissected using spatial transcriptomics, computational analyses, and functional assays. The results showed that pleiotrophin regulates mouse SSC functions through syndecan receptors, and ephrin-A1 may be a niche factor that influences human SSC functions. Moreover, the spatial re-distribution of inflammation-related LR interactions was found to underlie diabetes-induced testicular injury. This study provides a systems approach to understanding the complex organization of the stem cell microenvironment in health and disease.