Computational Approaches in Spatial Transcriptomics for the Study of Mammalian Spermatogenesis

Spermatogenesis is a complex and dynamic cellular differentiation process critical to male fertility. Although the full continuum of gene expression patterns from spermatogonial stem cells (SSCs) to spermatozoa in steady state was characterized using single-cell RNA sequencing technologies, the transcriptional dynamics of spermatogenesis within its native tissue context was largely unexplored. The recent development of spatial transcriptomics (ST) technologies has transformed male fertility research from a single-cell level to a two-dimensional spatial coordinate system and facilitated the study of spermatogenesis in the native environment of both the rodent and human testes. The spatial gene expression information generated by these ST technologies requires new computational approaches to extract novel biological insights. These requirements include, but are not limited to, spatial mapping of testicular cell types, identifying spatially variable genes, and understanding the molecular cross-talk between testicular cell types. Here, we review computational approaches that have been used to dissect mammalian spermatogenesis in the context of ST. We also highlight new computational approaches that can be leveraged to reveal novel insights into male fertility.