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Levels of p53 expression determine the competitive ability of embryonic stem cells during the onset of differentiation

Salvador Perez Montero, Sarah Bowling, View ORCID ProfileRubén Pérez-Carrasco, View ORCID ProfileTristan A. Rodriguez
doi: https://doi.org/10.1101/2022.02.28.482311
Salvador Perez Montero
1National Heart and Lung Institute, Imperial College London, UK
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Sarah Bowling
1National Heart and Lung Institute, Imperial College London, UK
2Stem Cell Program, Boston Children’s Hospital, Boston, MA, USA and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
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Rubén Pérez-Carrasco
2Stem Cell Program, Boston Children’s Hospital, Boston, MA, USA and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
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  • ORCID record for Rubén Pérez-Carrasco
  • For correspondence: r.perez-carrasco@imperial.ac.uk tristan.rodriguez@imperial.ac.uk
Tristan A. Rodriguez
1National Heart and Lung Institute, Imperial College London, UK
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  • ORCID record for Tristan A. Rodriguez
  • For correspondence: r.perez-carrasco@imperial.ac.uk tristan.rodriguez@imperial.ac.uk
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ABSTRACT

During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality control mechanism that contributes to this balance by eliminating viable cells that are less-fit than their neighbours. What mutations confer cells with a competitive advantage or the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are super-competitors that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependant, as does not occur when cells are pluripotent and is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through a competition for space or nutrients, but instead is mediated by short range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 01, 2022.
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Levels of p53 expression determine the competitive ability of embryonic stem cells during the onset of differentiation
Salvador Perez Montero, Sarah Bowling, Rubén Pérez-Carrasco, Tristan A. Rodriguez
bioRxiv 2022.02.28.482311; doi: https://doi.org/10.1101/2022.02.28.482311
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Levels of p53 expression determine the competitive ability of embryonic stem cells during the onset of differentiation
Salvador Perez Montero, Sarah Bowling, Rubén Pérez-Carrasco, Tristan A. Rodriguez
bioRxiv 2022.02.28.482311; doi: https://doi.org/10.1101/2022.02.28.482311

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