A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis

Area of Science:

• Reproductive biology
• Stem cell research
• Developmental biology

Background:

• Undifferentiated spermatogonia (Aundiff) in mouse testis possess spermatogenic stem cell (SSC) potential.
• GFRα1+ Aundiff cells are crucial for maintaining the self-renewing pool during homeostasis.
• The functional basis of heterogeneity and its impact on SSC dynamics are not fully understood.

Purpose of the Study:

• To investigate the heterogeneity of SSC subpopulations.
• To elucidate the functional basis and dynamics of SSC heterogeneity in maintaining spermatogenesis.
• To understand how SSC states influence self-renewal and differentiation.

Main Methods:

• Quantitative lineage tracing of SSC subpopulations.
• Analysis of cell surface markers (GFRα1, Plvap, Sox3) to define SSC states.
• Monitoring cell division rates and interconversion between states.

Main Results:

• An ensemble of heterogeneous SSC states supports homeostatic and persistent spermatogenesis.
• SSCs dynamically interconvert between a renewal-biased Plvap+/GFRα1+ state and a differentiation-primed Sox3+/GFRα1+ state.
• Slower division of Plvap+/GFRα1+ cells and faster division of Sox3+/GFRα1+ cells reduce mutation risk and maintain SSC density.

Conclusions:

• SSC heterogeneity is robustly maintained through stochastic state interconversion.
• Stem cell commitment is a gradual process involving licensed but uncommitted states.
• Differential cell-cycle dynamics in SSC subpopulations optimize stem cell pool maintenance and genomic integrity.