Title:  Cell motility enables stem cell density-dependent feedback and spatial order during resizing of an adult organ


Abstract:  How do tissues that are made up of multiple cell types regulate its various cell populations?  In particular, many stem cell-based tissues can resize drastically due to changing external input; for example, muscles expand when animals exercise, and guts expand when animals eat.  Often, the resizing dynamics involve an interplay between different cell types.  Using the intestine of the fruit fly, I study cellular behaviors and dynamics that regulate cell populations during tissue resizing.  Specifically, the fly gut expands four-fold in the number of mature cells and, proportionally, the number of stem cells when the animal eats.  I will present a biophysical model of the fly gut that captures this resizing.  Importantly, using a differential equations description of growth, the experimental kinetics of growth can be recapitulated by a description of feedback that depends on stem cell density.  A 2D simulation reveals that both this feedback and stem cell scaling can be achieved as long as stem cells exhibit a large enough amplitude of random cellular motion (`stem cell motility') and explore a large enough `territory' in their lifetime.  The notion that individual cells can obtain feedback information from the tissue by physically moving through it is suggested by live-imaging experiments.  Here, we see that stem cells are indeed motile in the fly gut, as cells show morphological signatures of active crawling.  Intriguingly, in the real system, we also see that stem cells have an ordered spatial distribution.  Here, genetic disruption of proteins associated with motility also disrupts the spatial order of stem cells, suggesting that cell motility is needed for order.  Together, these models and experiments involving cell motility point to a view that stem cells in solid tissues regulate their own populations and the overall tissue by physical exploration of nearby space.