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Updated: Oct 29, 2025
Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos
Published on: February 22, 2016
Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse
Ana Lima1,2, Gabriele Lubatti3,4,5, Jörg Burgstaller6
1National Heart and Lung Institute, Imperial College London, London, UK.
Abstract:
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.
Insights
Cell competition eliminates mouse epiblast cells with mitochondrial defects before gastrulation. This quality-control mechanism optimizes mitochondrial function by removing cells with DNA sequence changes.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Cell competition is a key quality-control mechanism eliminating unfit cells during development and in adults.
- The specific triggers and identities of cells eliminated by cell competition are not fully understood.
- A significant proportion of mouse epiblast cells undergo elimination prior to gastrulation.
Purpose of the Study:
- To investigate the nature of cells eliminated by cell competition during early mouse development.
- To identify the triggers and molecular hallmarks of cell elimination.
- To understand the role of mitochondrial function in cell competition.
Main Methods:
- Single-cell transcriptional profiling of eliminated mouse epiblast cells.
- Experimental manipulation of mitochondrial function.
- Analysis of mitochondrial DNA sequences (mt-Rnr1 and mt-Rnr2).
Main Results:
- Cells with mitochondrial defects are eliminated via cell competition in early mouse development.
- Mitochondrial defects are a common feature across various eliminated cell types.
- Altering mitochondrial function can induce cell competition.
- Sequence variations in mitochondrial DNA, even non-pathological ones, trigger cell competition.
Conclusions:
- Cell competition acts as a purifying selection process to ensure optimal mitochondrial performance in the developing mouse embryo.
- Mitochondrial integrity is critical for cell survival during pre-gastrulation development.
- This study reveals a novel link between mitochondrial DNA sequence and cell elimination through competition.
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