Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner
August 10, 2015
The Piddini group is studying how a self-renewing tissue can maintain its health when its constituent cells become less fit with age or due to accidental damage. Other work has shown that in developing tissues, cells compare their fitness with neighbours and the less fit cells are eliminated through cell competition, whereby the subfit cells die. But what happens in an adult tissue that is constantly renewing itself from a stem cell population, if some of the cells are sub-optimally fit? Do the less fit cells disappear at the same rate as healthy cells as part of normal turnover, or is there an active process targeting them for removal? The answers have potential impact for understanding both disease and ageing.
The model system for these studies was the adult fruit fly (Drosophila) gut, a simple epithelial layer with high cell turnover, maintained by a pool of stem cells. The team created mutant flies in which a proportion of these cells were less fit.
Using lineage tracing and biophysical modelling, the team, in collaboration with Ben Simons, followed what happened to the clones of healthy and mutant cells as they grew together in different combinations. The results show that the presence of healthy cells led to extinction of subfit cells, by induced cell death (‘apoptosis’) in differentiated cells and possibly by forcing differentiation rather than cell death in stem cells. At the same time, the cell competition induces stem cell proliferation and self-renewal in healthy tissue. Chemical signals from the less fit cells appear to fuel this effect. This process is therefore an adult equivalent of the cellular competition observed in developing tissues, and could help delay the insurgence of disease and ageing.
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