Mutation of p53 increases the competitive ability of pluripotent stem cells.
Development
; 151(2)2024 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-38131530
ABSTRACT
During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality-control mechanism that contributes to this balance by eliminating viable cells that are less fit than their neighbours. The mutations that confer cells with a competitive advantage and the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are 'super-competitors' that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependent, as it does not occur when cells are pluripotent and it is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through competition for space or nutrients, but instead is mediated by short-range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Communication
/
Pluripotent Stem Cells
Language:
En
Journal:
Development
Journal subject:
BIOLOGIA
/
EMBRIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Reino Unido