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Lima, A.* ; Lubatti, G. ; Burgstaller, J.* ; Hu, D.* ; Green, A.P.* ; di Gregorio, A.* ; Zawadzki, T.* ; Pernaute, B.* ; Mahammadov, E. ; Perez-Montero, S.* ; Dore, M.* ; Sanchez, J.M.* ; Bowling, S.* ; Sancho, M.* ; Kolbe, T.* ; Karimi, M.M.* ; Carling, D.* ; Jones, N.* ; Srinivas, S.* ; Scialdone, A. ; Rodriguez, T.A.*

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

Nat. Metab., DOI: 10.1038/s42255-021-00422-7 (2021)
DOI Order publishers version
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Pathogenic Mtdna Mutations; Embryonic Stem-cells; Stress-response; Dna Heteroplasmy; Segregation; Quantification; Division; Platform; Disease; Models
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Publisher Springer
Publishing Place London
Reviewing status Peer reviewed
Grants BBSRC
MRC
British Heart Foundation (BHF)
Helmholtz Association
BHF centre of excellence PhD studentship
Wellcome
Wellcome Trust