Non-cell-autonomous regulation of testicular stem cell niche homeostasis by the 20S proteasome core particle through cell adhesion and cyclin proteins

The Drosophila stem cell niche harbours two principal stem cell populations: germline stem cells (GSCs) and cyst stem cells (CySCs), whose self-renewal and differentiation are stringently governed by niche-derived regulatory factors. Nevertheless, the mechanistic role of the 20S core particle (CP)-the catalytic core of the 26S proteasome-within this niche remains poorly elucidated. In this study, we reveal that three 20S CP subunits, Prosα5, Prosβ2 and Prosβ5, mediate non-cell autonomous effects in the niche. Loss of function of Prosα5, Prosβ2 or Prosβ5 in cyst cells disrupts CySC differentiation, impairs early-stage germline differentiation and culminates in testicular dysgenesis, aberrant GSC-like cluster formation and male sterility. Moreover, we establish that diminished levels of these proteasome subunits trigger the accumulation of cell adhesion molecules and Cyclin proteins. Collectively, our findings offer novel insights into the regulatory functions of the 20S CP within the Drosophila testicular stem cell niche.