Metabolic Regulation in the Maintenance of Drosophila Testis Stem Cells

Stem cells maintain tissue homeostasis through precisely regulated self-renewal and differentiation, processes largely dependent on metabolic control. The Drosophila testis provides an ideal model system to study metabolism regulation of stem cell homeostasis due to many advantages, including its well-defined stem cell niche architecture and genetic tractability. Recent studies have revealed that germline stem cells (GSCs) and somatic cyst stem cells (CySCs) exhibit distinct metabolic profiles. In particular, GSCs exhibit a metabolic feature closely associated with mitochondrial dynamics, lipid metabolism, and redox homeostasis, all of which are essential for maintaining their stem identity through the regulation of TOR (Target of Rapamycin) signaling. Nutrient sensing through the insulin/TOR, BMP, and JAK-STAT pathways integrates nutritional cues with developmental programs. Lipid metabolism and membrane homeostasis further contribute to the maintenance of stem cells. Metabolic intermediates function as signaling molecules, modulating niche-stem cell interactions and epigenetic modifications in stem cells. Hence, dysregulation of metabolic homeostasis can lead to stem cell depletion and age-related reproductive decline. This review synthesizes the current understanding of metabolic regulation in Drosophila testis stem cell maintenance, identifies critical knowledge gaps, and explores future research directions such as spatial/temporal metabolomics approaches. Lastly, we highlight how these insights may help understand mammalian stem cell biology and regenerative medicine.