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: A second hallmark of cell competition is that it results in fitter cells taking over the tissue at the expense of less fit cells (Morata and Ripoll, 1975). Therefore, we asked whether wild-type and M−/+ cells would reciprocally affect their colonization and clone survival probabilities in this tissue. To address this, we generated M−/+ guts in which we labeled a subset of M−/+ ISCs (and their progeny) while at the same time inducing labeled wild-type ISCs (Figures 2A and 2B). We then compared clone survival frequencies between the two genotypes at 9 and 15 days after clone induction (ACI; expressed as a fraction of the average number of clones observed 4 days ACI). We also compared the survival frequency of competing M−/+ clones to that of neutral M−/+ clones (in wholly M−/+ guts). As shown in Figure 2C, the survival frequency of M−/+ clones was markedly lower than that of wild-type clones in the same guts, showing clonal disadvantage. Importantly, it was also lower than that of neutral M−/+ clones, indicating that the presence of wild-type clones negatively impacts on the survival probability of competing M−/+ cells. Consistently, this was also accompanied by a trend toward M−/+ clone attrition under competing conditions (Figure 2D).
Affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.