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Distinct modes of cell competition shape mammalian tissue morphogenesis.

ABSTRACT: Cell competition-the sensing and elimination of less fit 'loser' cells by neighbouring 'winner' cells-was first described in Drosophila. Although cell competition has been proposed as a selection mechanism to optimize tissue and organ development, its evolutionary generality remains unclear. Here, by using live imaging, lineage tracing, single-cell transcriptomics and genetics, we identify two cell competition mechanisms that sequentially shape and maintain the architecture of stratified tissue during skin development in mice. In the single-layered epithelium of the early embryonic epidermis, winner progenitors kill and subsequently clear neighbouring loser cells by engulfment. Later, as the tissue begins to stratify, the basal layer instead expels losers through upward flux of differentiating progeny. This cell competition switch is physiologically relevant: when it is perturbed, so too is barrier formation. Our findings show that cell competition is a selective force that optimizes vertebrate tissue function, and illuminate how a tissue dynamically adjusts cell competition strategies to preserve fitness as its architectural complexity increases during morphogenesis.

SUBMITTER: Ellis SJ

PROVIDER: S-EPMC6638572 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Distinct modes of cell competition shape mammalian tissue morphogenesis

Project description:Cell competition (CC)—the sensing and elimination of less fit “loser” cells by neighbouring “winner” cells—was first described in Drosophila. Although proposed as a selection mechanism to optimize tissue and organ development, its evolutionary generality remains unclear. Here, by employing live-imaging, lineage-tracing, single cell transcriptomics and genetics, we unearth two intriguing CC mechanisms that sequentially shape and maintain stratified tissue architecture during mouse skin development. Early in embryonic epidermis, winner progenitors within the single-layered epithelium kill and clear neighbouring losers by engulfment. Upon stratification and skin barrier formation, the basal layer instead expels losers through a homeostatic upward flux of differentiating progeny. This CC switch is physiologically relevant, as when it is perturbed, so too is barrier formation. Our findings establish CC as a selective force to optimize function of a vertebrate tissue, but also illuminate how a tissue dynamically adjusts its CC strategies to preserve fitness as it encounters increased architectural complexity during morphogenesis.

2019-05-31 | GSE128241 | GEO

Distinct modes of cell competition shape mammalian tissue morphogenesis

Project description:Distinct modes of cell competition shape mammalian tissue morphogenesis

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Unravelling the distinct contribution of cell shape changes and cell intercalation to tissue morphogenesis: the case of the <i>Drosophila</i> trachea.

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Forces generated by cell intercalation tow epidermal sheets in mammalian tissue morphogenesis.

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Spontaneous Cell Competition in Immortalized Mammalian Cell Lines.

Project description:Cell competition is a form of cell-cell interaction by which cells compare relative levels of fitness, resulting in the active elimination of less-fit cells, "losers," by more-fit cells, "winners." Here, we show that in three routinely-used mammalian cell lines - U2OS, 3T3, and MDCK cells - sub-clones arise stochastically that exhibit context-dependent competitive behavior. Specifically, cell death is elicited when winner and loser sub-clones are cultured together but not alone. Cell competition and elimination in these cell lines is caspase-dependent and requires cell-cell contact but does not require de novo RNA synthesis. Moreover, we show that the phenomenon involves differences in cellular metabolism. Hence, our study demonstrates that cell competition is a common feature of immortalized mammalian cells in vitro and implicates cellular metabolism as a mechanism by which cells sense relative levels of "fitness."

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