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Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner.

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Suijkerbuijk, Saskia JE 
Poirier, Enzo Z 
Mansour, Sarah 


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. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem cell and tissue population dynamics. We show that healthy cells induce clonal extinction in weak tissues, targeting both stem and differentiated cells for elimination. 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.



Adult Stem Cells, Animals, Cell Differentiation, Cell Lineage, Cell Proliferation, Drosophila Proteins, Drosophila melanogaster, JNK Mitogen-Activated Protein Kinases, Janus Kinases, MAP Kinase Signaling System, Ribosomes, STAT Transcription Factors, Transcription Factors

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Dev Cell

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Elsevier BV
Wellcome Trust (098357/Z/12/Z)
Cancer Research Uk (None)
Wellcome Trust (092096/Z/10/Z)
Netherlands Organisation for Scientific Research (NWO) (File No: 82512027)
Cancer Research Uk (None)
This work was supported by a Cancer Research UK Programme Grant (E.P. and G.K. A12460), a Royal Society University Research fellowship to E.P. (UF090580), an EMBO Long-Term Fellowship (ALTF 1476-2012), NWO Rubicon grant (825.12.027) and a Dutch Cancer Society Fellowship (BUIT-2013-5847) to S.J.E.S, a Wellcome Trust PhD studentships to IK and Core grant funding from the Wellcome Trust Core (092096) and CRUK (C6946/A14492).