Title: Unique metabolic demands of the germline stem cell lineage: glycolysis is required for stem cell maintenance and egg chamber growth, but not mitotic proliferation, meiotic entry, nor oocyte specification
Abstract: Stem cells and their differentiating progeny adopt distinct metabolisms to fulfill their unique roles. However, the specific metabolic requirements along stem cell lineages in the context of whole living organisms, where complex tissues can house multiple stem cell types, remains largely unexplored. In the Drosophila ovary, two contrasting stem cell lineages, germline and follicle stem cells, interact intricately and are highly regulated by diet. Germline stem cells (GSCs) divide to give rise to cystoblasts that undergo four mitotic divisions to form 16-cell cysts that undergo drastic differentiation into mature oocytes. Follicle stem cells and their progeny comprise a more conventional somatic lineage. In this study, we defined the cell-specific metabolic requirements for glycolysis and fatty acid oxidation in both lineages using FLP/FRT-mediated genetic mosaic analysis. Remarkably, fatty acid oxidation is largely dispensable in both stem cell lineages under normal conditions. By contrast, glycolysis is crucial for GSC maintenance and 16-cell cyst survival, in addition to being required for more differentiated egg chamber development and survival. Surprisingly, glycolysis is not required for GSC or cyst proliferation, entry into meiosis, or oocyte specification, suggesting distinct metabolic requirements. Follicle stem cells and their earliest progeny require glycolysis for survival but not proliferation, while more differentiated follicle cells require glycolysis for proliferation. Future studies will address the mechanistic basis for these requirements, what alternative metabolic requirements are at play, metabolic crosstalk between the stem cell lineages, and how requirements change under different physiological conditions, such as exercise and nutrient scarcity.
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