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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. 3, 1091-1108 (2021)
Postprint DOI PMC
Open Access Green
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Pathogenic Mtdna Mutations; Embryonic Stem-cells; Stress-response; Dna Heteroplasmy; Segregation; Quantification; Division; Platform; Disease; Models
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Zeitschrift Nature metabolism
Quellenangaben Band: 3, Heft: 8, Seiten: 1091-1108 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epigenetics and Stem Cells (IES)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Stem Cell and Neuroscience
PSP-Element(e) G-506290-001
G-506200-001
Förderungen BBSRC
MRC
British Heart Foundation (BHF)
Helmholtz Association
BHF centre of excellence PhD studentship
Wellcome
Wellcome Trust
DOI 10.1038/s42255-021-00422-7
WOS ID WOS:000672838400001
Scopus ID 85110486433
PubMed ID 34253906
Erfassungsdatum 2021-07-22
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