Cell competition: the winners and losers of fitness selection

Abstract

The process of cell competition results in the elimination of cells that are viable but 'less fit' than surrounding cells. Given the highly heterogeneous nature of our tissues, it seems increasingly likely that cells are engaged in a 'survival of the fittest' battle throughout life. The process has a myriad of positive roles in the organism: it selects against mutant cells in developing tissues, prevents the propagation of oncogenic cells and eliminates damaged cells during ageing. However, 'super-fit' cancer cells can exploit cell competition mechanisms to expand and spread. Here, we review the regulation, roles and risks of cell competition in organism development, ageing and disease.

Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition

“…The ability of 41 cells to influence their neighbouring cells' fate choices has become apparent from 42 studies in various in vitro and in vivo models. An example of this is cell competition, a 43 type of cell-cell interaction wherein viable but less-fit "loser" cells are outcompeted 44 for nutrients or space and eventually eliminated by the fitter "winner" cells (reviewed 45 in (Bowling et al, 2019)). Initially described and studied in Drosophila as a tissue 46 homeostatic mechanism (Morata and Ripoll, 1975), over recent years it has become 47 evident that a form of cell competition, known as super-competition, is implicated in 48 expansion of cancerous cells (Eichenlaub et al, 2016;Suijkerbuijk et al, 2016).…”

“…The elimination of wild-type cells which occurred in co-culture with variant 124 cells is reminiscent of cell competition described in many different systems, whereby 125 'weaker' loser cells are eliminated in the presence of 'fitter' winner cells (reviewed in 126 (Bowling et al, 2019)). Cell competition typically involves inducing either senescence 127 (Bondar and Medzhitov, 2010) or apoptosis (Brumby and Richardson, 2003;Moreno 128 et al, 2002;Sancho et al, 2013) in loser cells.…”

Chronic Interleukin-1 exposure triggers selective expansion ofCebpa-deficient multipotent hematopoietic progenitors

“…interact with microenvironmental factors (IL-1β) and other cells within its niche. Cell competition dynamics are appreciated to be an important factor in tumorigenesis (Bowling et al, 2019). We hypothesized that WT competitor MPP3 would exhibit differential gene expression in competition against a more fit population (vs. Cebpa Δ/Δ MPP3 in chronic IL-1β) versus in neutral competition (vs. Cebpa +/+ MPP3 in chronic IL-1β), even though they are identical by genotype and treatment.…”

Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition

“…This observation led to the concept of "cell competition" in which a given cell compares its fitness to that of its neighboring cells. Cells with a relatively higher fitness level survive, whereas cells with a relatively lower fitness level are eliminated by either apoptosis or apical extrusion (Baker, 2017;de Beco, Ziosi, & Johnston, 2012;Bowling, Lawlor, & Rodriguez, 2019;Claveria & Torres, 2016;Madan, Gogna, & Moreno, 2018;Morata & Calleja, 2019;Wagstaff, Kolahgar, & Piddini, 2013). Cell competition is now a well-established process among mammalian "cell societies" as well.…”

“…In Drosophila, cell competition can be induced by activation of proto-oncogenes such as Myc, Ras and Src, as well as that of genes regulating cellular apicobasal polarity such as Scribble and Discs large (Dlg) (Baker, 2017;de Beco et al, 2012;Bowling et al, 2019;Claveria & Torres, 2016;Madan et al, 2018;Morata & Calleja, 2019;Nagata & Igaki, 2018;Wagstaff et al, 2013). In the developing mouse embryo, cells with low levels of Myc undergo apoptosis if in proximity to cells with higher Myc levels (Claveria, Giovinazzo, Sierra, & Torres, 2013;Sancho et al, 2013).…”