Abstract
SummaryThroughout 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.
Highlights
In adult animals, homeostatic tissues are composed of stem cells and differentiated cells that carry out specific tissue functions
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 find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization
Summary
Homeostatic tissues are composed of stem cells and differentiated cells that carry out specific tissue functions. It is well established that in developing tissues, cells compare their fitness with their neighbors, and less fit (‘‘loser’’) cells are eliminated through a phenomenon known as cell competition (Morata and Ripoll, 1975; de Beco et al, 2012; Vivarelli et al, 2012; Vincent et al, 2013) This likely acts as a quality control mechanism that eliminates less fit cells before they can contribute to the adult organism. Cell competition has been observed between wild-type cells and cells overexpressing myc in the mouse heart (Villa del Campo et al, 2014) This phenomenon has been observed in some adult niche compartments (Jin et al, 2008; Issigonis et al, 2009; Rhiner et al, 2009; Bondar and Medzhitov, 2010; Marusyk et al, 2010), and a recent report suggests that it may be taking place in adult fly tissues (Merino et al, 2015). We took advantage of the simplicity and genetic tractability of a well-defined model of adult homeostatic tissue, the Drosophila adult posterior midgut, to study the effect of cell competition on stem and differentiated cells and its consequences on tissuelevel population dynamics
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