Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner.
Bottom Line: Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues.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.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: Our data show that when cells of different fitness coexist in the adult fly gut, weak cells undergo frequent cell death whereas fit cells boost their tissue-colonization ability. Cell death is known to stimulate proliferation in nearby cells in several tissues, including the fly gut, through a phenomenon known as compensatory proliferation (Fan and Bergmann, 2008; Amcheslavsky et al., 2009). In addition, inhibiting cell death has been shown to block the overproliferation of fit cells during cell competition (de la Cova et al., 2004, 2014; Li and Baker, 2007). We therefore wondered whether protecting M−/+ cells from cell competition-induced apoptosis could mitigate the overgrowth of wild-type clones. Interestingly, we found that expressing the apoptosis inhibitor Diap1, which can effectively inhibit cell death in this tissue (Figures S3A–S3D), did not reduce the overgrowth of wild-type cells, whether it was expressed in ECs (Figure S3E) or expressed in both ECs and progenitor cells (Figures S3F and S3G). This suggested that signals other than apoptosis-induced proliferation might be involved. It has been reported that several mutants whose cells are outcompeted by wild-type cells, including M−/+, display chronic activation of the JNK signaling pathway in wing imaginal discs (Tamori and Deng, 2011). We therefore asked whether in the midgut, M−/+ cells also display increased JNK signaling. Indeed, we observed higher expression of puc-LacZ, a transcriptional reporter of JNK activation, in M−/+ midguts compared to control guts (Figures 5A and 5B), indicating that the pathway was activated.
Affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.