Cell Competition

Abstract

Cell competition is a conserved mechanism by which unfit cells are outcompeted by fitter neighbours. This quality control mechanism allows the maintenance and propagation of fitter cells, by potentiating the elimination of unfit cells from tissues. Cell competition plays a central role during embryogenesis and in adulthood, contributing to proper development and preservation of tissues homeostasis. The absence of fitness control impacts organ function, which ultimately results in shorten lifespan and disease development. In fact, impairment of cell competition or the appropriation of this process by pre‐malignant cells can allow the expansion of potentially dangerous cells leading to tumorigenesis. Different molecular mechanisms and strategies have been described to be required for the elimination of unfit cells depending on the tissue context and genetics. Key Concepts Cell competition actively takes place since embryonic stages, throughout development and in the adult. Cell competition is a conserved mechanism in multicellular animals. When in the presence of fitter cells, unfit cells are eliminated from tissues by cell competition. The context and genes involved determine the mechanism by which loser cells are eliminated. Selection of fit cells to be maintained in tissues promote homeostasis and improves lifespan. Accumulation of viable but less fit cells is detrimental for the organism. Pre‐malignant cells may hijack the cell competition mechanism, leading to tumour initiation.

Cell competition from development to neurodegeneration

“…1 B) ( Brás-Pereira and Moreno, 2018 ; Eisenhoffer et al, 2012 ; Levayer et al, 2016 ; Marinari et al, 2012 ; Norman et al, 2012 ; Shraiman, 2005 ; Wagstaff et al, 2016 ) and fitness fingerprints-mediated cell competition ( Fig. 1 C) ( Coelho et al, 2018 ; Coelho and Moreno, 2020 ; Costa et al, 2020 ; Madan et al, 2019 ; Merino et al, 2013 , 2016 ; Rhiner et al, 2010 ), which we discuss in detail in this Review.

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“…Cancer has also been linked to cell competition ( Costa et al, 2020 ; Di Gregorio et al, 2016 ; Kim and Jain, 2020 ; Petrova et al, 2012 ). Fitness fingerprints-mediated cell competition has also been identified in mammals, in the context of cancer, and will be further reviewed in ‘The Flower code in cell competition’ section, below.…”