Developmental Cell
Volume 34, Issue 3, 10 August 2015, Pages 297-309
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Article
Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner

https://doi.org/10.1016/j.devcel.2015.06.010Get rights and content
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Highlights

  • In the adult fly gut, wild-type cells outcompete subfit Minute−/+ cells

  • Both stem and differentiated Minute−/+ cells are eliminated by cell competition

  • Cell competition promotes proliferation and self-renewal of normal stem cells

  • The growth of healthy cells is boosted by JAK-STAT signaling

Summary

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.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

2

Present address: Viral Populations and Pathogenesis, Institut Pasteur, CNRS UMR 3569, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France

3

Present address: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany