Open AccessCell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development
Author(s) -
Ana Lima,
Gabriele Lubatti,
Joerg P. Burgstaller,
Di Hu,
Alistair P Green,
Aida Di Gregorio,
Tamzin Zawadzki,
Bárbara Pernaute,
Elmir Mahammadov,
Salvador Pérez-Montero,
Marian Dore,
Juan Miguel Sánchez,
Sarah Bowling,
Margarida Sancho,
Thomas Kolbe,
Mehdi Karimi,
David Carling,
Nick Jones,
Shankar Srinivas,
Antonio Scialdone,
Tristan A. Rodríguez
Publication year - 2021
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-021-00422-7
Subject(s) - epiblast , gastrulation , microbiology and biotechnology , biology , cell , mitochondrial dna , mitochondrion , embryo , genetics , embryogenesis , gene
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 mice, 35% of epiblast cells are eliminated before gastrulation. Here we show that cells with mitochondrial defects are eliminated by cell competition during early mouse development. Using single-cell transcriptional profiling of eliminated mouse epiblast cells, we identify hallmarks of cell competition and mitochondrial defects. We demonstrate that mitochondrial defects are common to a range of different loser cell types and that manipulating mitochondrial function triggers cell competition. Moreover, we show that in the mouse embryo, cell competition eliminates cells with sequence changes in mt-Rnr1 and mt-Rnr2, and that even non-pathological changes in mitochondrial DNA sequences can induce cell competition. Our results suggest that cell competition is a purifying selection that optimizes mitochondrial performance before gastrulation.