Regulation of stem cell quiescence and activity in the adult brain
Dr Francois GUILLEMOT
The Francis Crick Institute, London, Royaume-Uni
mardi 17 octobre 2017 - 11h00
- Auditorium, IGBMC
Invité(e) par Pascal DOLLE & Muriel RHINN
Neural stem cells located in restricted regions of the adult brain produce neurons that have important functions in memory and mood control. While the niche signals that control neural stem cells fates have been extensively investigated, little is known of the intrinsic mechanisms that mediate the activity of these extrinsic signals and implement appropriate fate decisions. Using high throughput genomic analysis and genetic approaches in stem cell cultures and in vivo, we characterise transcription factors that regulate the transitions between neural stem cell quiescence, activation and differentiation in response to niche signals.
We previously found that expression of the transcription factor Ascl1 by stem cells of the adult hippocampus is essential for their activation. We now show that regulation of Ascl1 protein levels determines the rates at which stem cells self-renew and new neurons are produced. Reduced levels of Ascl1 slow down stem cell proliferation and neurogenesis whereas increased levels accelerate proliferation and lead eventually to stem cell exhaustion and inhibition of neurogenesis. Ascl1 protein levels in are controlled by several mechanisms involving the E3 ubiquitin ligase Huwe1 in proliferating stem cells and the transcriptional repressor Id4 in quiescent stem cells. We currently investigate the nature of the hippocampal niche signals that employ these mechanisms to regulate stem cell activity.