Cell competition modifies adult stem cell and tissue population dynamics in a JAKSTAT dependent manner
Suijkerbuijk, Saskia JE
Poirier, Enzo Z
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Kolahgar, G., Suijkerbuijk, S. J., Kucinski, I., Poirier, E. Z., Mansour, S., Simons, B., & Piddini, E. (2015). Cell competition modifies adult stem cell and tissue population dynamics in a JAKSTAT dependent manner. Developmental Cell, 34 297-309. https://doi.org/10.1016/j.devcel.2015.06.010
Through 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 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 fuelled by the JAK-STAT ligand Unpaired-3, produced by Minute-/+ cells in response to chronic JNK stress signaling.
Cell competition, Drosophila, stem cells, tissue homeostasis, inflammatory response, posterior midgut, ribosomopathies, self-renewal, cell death, JNK signaling, JAK-STAT signaling, Minute
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).
WELLCOME TRUST (098357/Z/12/Z)
Cancer Research UK (12460)
Wellcome Trust (092096/Z/10/Z)
Cancer Research UK (A14492)
Netherlands Organisation for Scientific Research (NWO) (File No: 82512027)
External DOI: https://doi.org/10.1016/j.devcel.2015.06.010
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248694