PT  - JOURNAL ARTICLE
AU  - Ana Lima
AU  - Gabriele Lubatti
AU  - Jörg Burgstaller
AU  - Di Hu
AU  - Alistair Green
AU  - Aida Di Gregorio
AU  - Tamzin Zawadzki
AU  - Barbara Pernaute
AU  - Elmir Mahammadov
AU  - Marian Dore
AU  - Juan Miguel Sanchez
AU  - Sarah Bowling
AU  - Margarida Sancho
AU  - Mohammad Karimi
AU  - David Carling
AU  - Nick Jones
AU  - Shankar Srinivas
AU  - Antonio Scialdone
AU  - Tristan A. Rodriguez
TI  - Differences in mitochondrial activity trigger cell competition during early mouse development
AID  - 10.1101/2020.01.15.900613
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.15.900613
4099  - http://biorxiv.org/content/early/2020/01/15/2020.01.15.900613.short
4100  - http://biorxiv.org/content/early/2020/01/15/2020.01.15.900613.full
AB  - Cell competition is emerging as a quality control mechanism that eliminates unfit cells in a wide range of settings from development to the adult. However, the nature of the cells normally eliminated by cell competition and what triggers their elimination remains poorly understood. Here we have performed single cell transcriptional profiling of early mouse embryos and find that the cells eliminated show the hallmarks of cell competition, are mis-patterned and have mitochondrial defects. We demonstrate that mitochondrial defects are common to a range of different loser cell types and that manipulating mitochondrial function is sufficient to trigger competition. Importantly, we show that in the embryo loser epiblast cells display mitochondrial DNA mutations and that even small changes in mitochondrial DNA sequence can influence the competitive ability of the cell. Our results therefore suggest that cell competition is a purifying selection that optimises metabolic output prior to gastrulation.