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To not love thy neighbor: mechanisms of cell competition in stem cells and beyond

Cell Death & Differentiation volume 30, pages 979–991 (2023)Cite this article

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Abstract

Cell competition describes the process in which cells of greater fitness are capable of sensing and instructing elimination of lesser fit mutant cells. Since its discovery in Drosophila, cell competition has been established as a critical regulator of organismal development, homeostasis, and disease progression. It is therefore unsurprising that stem cells (SCs), which are central to these processes, harness cell competition to remove aberrant cells and preserve tissue integrity. Here, we describe pioneering studies of cell competition across a variety of cellular contexts and organisms, with the ultimate goal of better understanding competition in mammalian SCs. Furthermore, we explore the modes through which SC competition takes place and how this facilitates normal cellular function or contributes to pathological states. Finally, we discuss how understanding of this critical phenomenon will enable targeting of SC-driven processes, including regeneration and tumor progression.

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Fig. 1: Schematic representation of cell competition.
Fig. 2: Examples of competitive cell elimination modes.
Fig. 3: Examples of cellular interactions during competition.
Fig. 4: Schematic representations of the bystander effect.

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Acknowledgements

We apologize to colleagues whose contributions we could not adequately cite due to space constraints. We thank Fuchs lab members for helpful discussion and input. Figures and graphical abstract were generated using BioRender.

Funding

YF was supported by the EMBO Young Investigator program, ICRF (15-771-RCDA) grants, ISF individual 2124/19, and IPMP 1019045 2029637 grants, and ICRF acceleration AG-17-917.

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Authors and Affiliations

  1. Laboratory of Stem Cell Biology and Regenerative Medicine, Department of Biology, Technion Israel Institute of Technology, Haifa, Israel

    Marianna Yusupova & Yaron Fuchs

  2. Lorry Lokey Interdisciplinary Center for Life Sciences & Engineering, Technion Israel Institute of Technology, Haifa, Israel

    Marianna Yusupova & Yaron Fuchs

  3. Augmanity, Rehovot, Israel

    Yaron Fuchs

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  1. Marianna Yusupova
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MY and YF wrote and approved the final paper.

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Correspondence to Yaron Fuchs.

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Yusupova, M., Fuchs, Y. To not love thy neighbor: mechanisms of cell competition in stem cells and beyond. Cell Death Differ 30, 979–991 (2023). https://doi.org/10.1038/s41418-023-01114-3

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  • DOI: https://doi.org/10.1038/s41418-023-01114-3

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