Testicular Spatial Transcriptome Atlas

Single-cell RNA sequencing has revealed extensive molecular diversity in gene programs governing mammalian spermatogenesis but fails to delineate their functional dynamics in the native context of seminiferous tubules which are the spatially-confined functional units of spermatogenesis. Here, we use a novel spatial transcriptomics technology Slide-seq to generate a comprehensive spatial atlas that captures the genome-wide gene expression dynamics and spatial gene expression pattern at near single-cell resolution in the mouse and human testis. By using the high-coverage Slide-seq data, we devise a computational framework that accurately pinpoints the spatial locations of testicular cell types in individual seminiferous tubules without prior knowledge. Unbiased spatial transcriptome analysis systematically identifies spatially patterned genes and gene programs, nominating genes with previously underappreciated but important functions in spermatogenesis. A comparison of the spatial atlas generated from the wild type and diabetic testis reveals a disruption in the spatial cellular organization in diabetic seminiferous tubules. Finally using the human testicular spatial atlas, we identify two spatially segregated spermatogonial populations composed of stem cells at distinct transcriptional states.