title: Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner.
abstract: 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.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Golnar
authors.initials: G
authors.lastname: Kolahgar
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Saskia J E
authors.initials: SJ
authors.lastname: Suijkerbuijk
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Iwo
authors.initials: I
authors.lastname: Kucinski
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Enzo Z
authors.initials: EZ
authors.lastname: Poirier
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mansour
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Electronic address: e.piddini@gurdon.cam.ac.uk.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Piddini
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D012270:Ribosomes / Q000235:genetics; D050791:STAT Transcription Factors / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; C115570:upd1 protein, Drosophila; D053612:Janus Kinases; C085845:hop protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases