Metabolism of neural stem cell – niche interactions

While almost all eukaryotic cells require mitochondrial energy production, not all cells and tissues are equally susceptible to mitochondrial disease. In our lab, we mainly study how mitochondrial dysfunction and mutations in the mitochondrial genome affect neural stem cell (NSC) behaviour in Drosophila and mouse. Our long-term aim is to better understand tissue-specific presentation of mitochondrial and neurodegenerative diseases and improve their treatment. 

We previously showed that NSCs in the Drosophila brain require mitochondrial activity for proliferation and temporal patterning. However, the impact of mitochondrial dysfunction on NSC behaviour is context-dependent. Using targeted genetic screening, scRNA-sequencing, genetically encoded metabolite sensors and ectopic enzyme expression, we revealed novel metabolic interactions between NSCs and their glial niche, and found that maintenance of the redox balance in glia can safeguard NSCs against the consequences of mitochondrial dysfunction. 

This suggests that metabolic vulnerability of cells within their tissue-context is not only determined by cell-type, but also by tissue composition and metabolic interactions with their surrounding niche. Elucidating such generic mechanisms of the tissue-wide response to mitochondrial dysfunction may lead to better understanding of the metabolic origin of neurodegenerative diseases and cancer.

Event poster