Identification of IL1R2 as a Spermatogonial Stem Cell-specific Sorted Protein in Humans and Mice

Self-renewal and differentiation of spermatogonial stem cell (SSCs) are critical for sustaining spermatogenesis in adult mammals. SSC populations are highly heterogeneous and dynamic, imposing great challenges in their isolation and functional characterization. The current study aimed to generate Il1r2CreERT2/+; Rosa26mTmG/+ mice to pulse-label Il1r2-expressing cells; through lineage tracing, we discovered that IL1R2+ SSCs, essential for spermiogenesis, possess long-term capacities of self-renewal and differentiation. Under injury-induced regenerative conditions, disruption of spermatogenesis can reactivate IL1R2+ SSCs for proliferation via the PI3K-AKT-mTOR pathway to replenish the SSC pool. We further validated our discovery by systematically characterizing both mouse and human IL1R2+ SSCs isolated. Our findings confirmed the important role of IL1R2+ SSCs in the maintenance of spermatogenesis and regeneration after spermatogenic injury; IL1R2 might serve as a promising marker for enriching human and mouse SSCs. Overall design: To characterize IL1R2+ SSCs, we isolated IL1R2+, THY1+, and c-KIT+ cells from mouse testes using FACS for RNA-Seq analysis