Speaker
Description
Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned. Importantly, even when assuming that all cells in a tissue are molecularly equivalent, we predict a universal functional dependence of the long-term clonal survival probability on distance from the niche, as well as the emergence of a well-defined number of functional stem cells, dependent only on the rate of random movements vs. mitosis-driven advection. We verify the predictions of this theory in multiple organs. This argues for a key role of positional fluctuations in dictating stem cell number and dynamics.
Moreover, in a second study, we investigate the mechanics of how intestinal crypt geometry arises itself, using intestinal organoids as a model system. We find through a combination of experiments and biophysical modelling that cell fate-specific changes in osmotic and actomyosin forces coordinate robust organoid morphogenesis.
[1] Corominas-Murtra et al, PNAS, 2020, Yang et al, bioRxiv, 2020
