Dissecting the spermatogonial stem cell niche using spatial transcriptomics

Area of Science:

• Reproductive biology
• Stem cell biology
• Molecular and cellular biology

Background:

• Spermatogonial stem cells (SSCs) are crucial for continuous sperm production throughout life.
• SSCs reside in specialized testicular niches that regulate their self-renewal and differentiation.
• The intricate molecular and cellular crosstalk within SSC niches is not fully understood.

Purpose of the Study:

• To comprehensively dissect the molecular, cellular, and spatial characteristics of SSC niches.
• To spatially map ligand-receptor (LR) interactions within mouse and human testes.
• To investigate the role of niche interactions in testicular health and disease, including diabetes-induced injury.

Main Methods:

• Integration of spatial transcriptomics, advanced computational analyses, and functional assays.
• Systematic dissection of the SSC niche microenvironment.
• Spatially resolved mapping of ligand-receptor interactions in mammalian testes.

Main Results:

• Identified pleiotrophin signaling via syndecan receptors as critical for mouse SSC function.
• Discovered ephrin-A1 as a potential regulator of human SSC function.
• Revealed that altered spatial distribution of inflammation-related LR interactions is associated with diabetes-induced testicular damage.

Conclusions:

• This study provides a systems-level understanding of SSC niche organization in both health and disease.
• The findings highlight specific LR interactions (pleiotrophin/syndecan, ephrin-A1) critical for SSC regulation.
• The research elucidates the impact of inflammation on testicular function and provides a framework for future studies on male infertility and regenerative medicine.