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Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development

By Ana Lima, Gabriele Lubatti, Jorg Burgstaller, Di Hu, Alistair Green, Aida di Gregorio, Tamzin Zawadzki, Barbara Pernaute, Elmir Mahammadov, Salvador Perez Montero, Marian Dore, Juan Miguel Sanchez, Sarah Bowling, Margarida Sancho, Mohammed Karimi, David Carling, Nick Jones, Shankar Srinivas, Antonio Scialdone, Tristan A Rodriguez

Posted 15 Jan 2020
bioRxiv DOI: 10.1101/2020.01.15.900613

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. In mouse, prior to gastrulation 35% of epiblast cells are eliminated. Here we have performed single cell transcriptional profiling of these cells and find that they show the hallmarks of cell competition 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 cell competition eliminates cells with mitochondrial DNA mutations and that even non-pathological changes in mitochondrial DNA sequence can induce cell competition. Our results therefore suggest that cell competition is a purifying selection that optimises mitochondrial performance prior to gastrulation.

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