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. [Display omitted] •Inference of ligand-receptor (LR) pairs at the spermatogonial stem cell niche•PTN and EPHA1 are potential niche factors•Spatial alteration of LR pair expression underlies diabetes-induced infertility Rajachandran et al. demonstrate how spatial transcriptomics can be leveraged to identify niche factors that regulate spermatogonial stem cell functions by mapping the ligand-receptor interaction landscape in mouse and human testes.