From stem cell interactions to tissue homeostasis: a multiscale approach
Nicolas Dray (Institut Pasteur)
Tissue homeostasis relies on the coordinated regulation of stem cell (SC) behaviors, including self-renewal, differentiation, and quiescence. Yet how stem cell fate decisions are coordinated across space and time to sustain long-term tissue stability remains largely unknown.
We hypothesize that local cell-cell communication through Notch signaling, coupled with tissue geometry and spatial organization, gives rise to self-sustained emergent properties at the tissue scale. To investigate this question, we combine experiments, spatial statistics, and multiscale modeling in the adult zebrafish pallium, a relatively simple and accessible system for studying neural stem cell in vivo.
Using multiplexed smFISH, immunohistochemistry, morphometric analysis, and intravital imaging, we quantify cell states, fate transitions, and tissue geometry at single-cell resolution. We are now developing methods to infer causal Notch gene regulatory networks from these data and to characterize stem cell interactions across scales using spatial statistical approaches.
I will present our recent progress and discuss our strategy to integrate these results into a multiscale model aimed at understanding how tissue homeostasis and multistability emerge from the interplay between cell-cell signaling, tissue topology, and cell fate decisions.