Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner.
Bottom Line: We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells.We also find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization.Finally, we show that winner cell proliferation is fueled by the JAK-STAT ligand Unpaired-3, produced by Minute(-/+) cells in response to chronic JNK stress signaling.
Affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.Show MeSH
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Mentions: Recent studies have shown that cell competition can also take place in adult tissues (Oertel et al., 2006; Villa del Campo et al., 2014). Our work has taken this notion forward and delineated quantitatively how adult stem cells and tissue population dynamics are affected by cell competition (Figure 7A). In the subfit population, differentiated cells are killed by apoptosis followed by cell delamination; stem cells are also eliminated, possibly via induction of differentiation, as we have not detected dying stem cells. In parallel, as we show, the healthy tissue expands due to an increase in stem cell proliferation and self-renewal. Indeed, biophysical modeling shows that changes in these parameters of a magnitude comparable to what we observe experimentally is sufficient to recapitulate the stem cell dynamics of wild-type tissue undergoing Minute cell competition. Interestingly, accelerated proliferation of fitter stem cells has been seen in mouse embryonic stem cells using in vitro models of cell competition (Clavería et al., 2013; Sancho et al., 2013). However, in those studies, increased stem cell self-renewal has not been observed, probably because stemness in vitro is artificially maintained by exogenous factors in the culture medium.
Affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.