Periodic Reporting for period 2 - StemCellHabitat (Metabolic and Timed Control of Stem Cell Fate in the Developing Animal)
Reporting period: 2019-08-01 to 2021-01-31
Although several aspects of stem cell biology are understood it is still not fully known how stem cells are directed to generate specific differentiated cells or how to efficiently regulate stem cell proliferation. This project aims at studying how stem cells are normally regulated during animal development according to their spatial, temporal and metabolic identity to determine their proliferation and the type of differentiated cells formed. To answer these questions, this project uses Drosophila melanogaster, an animal complex enough to be similar to higher eukaryotes and yet simple enough to dissect the mechanistic details of cell regulation and its impact on the organism. Drosophila has several stem cell populations all dynamically regulated during development and is thus a fantastic model to study stem cells. Using a multidisciplinary approach combining genetics, cell type/age sorting, multi-omics analysis, fixed and 3D-live stem cell imaging and metabolite dynamics, this project proposes an integrative approach to investigate how stem cells are regulated in the developing animal.
At the cell autonomous level, we have found that neural stem cell differentiation requires differential regulation of basal transcription. We have also identified many novel candidate regulators of neural stem cell fate and neuronal formation that will now be further analysed.
Stem cell fate has been described to be intricately connected with energy metabolism. Although energy metabolism occurs in several cellular compartments, it is in the mitochondria that an important fraction of all metabolic reactions occurs, including oxidative phosphorylation. We have explored how the metabolic regulation of stem cell fate is coordinated with mitochondrial activity and dynamics. We have found that mitochondrial dynamics in the Drosophila ovary regulates germ stem cell number, cell fate and female fertility.
We have also found many novel regulators of neural stem cell fate and neural fate commitment, which we will now explore.
It is our expectation to have a global molecular characterisation of the transcriptional and metabolic mechanisms involved in fate regulation during brain development.