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Spontaneous Cell Competition in Immortalized Mammalian Cell Lines
Alfredo I Penzo-Méndez1, Yi-Ju Chen1, Jinyang Li1
1Departments of Medicine and Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Cell competition, where fitter cells eliminate weaker ones, is common in lab-grown mammalian cells. This process, driven by metabolic differences, requires cell contact and caspases for elimination.
Area of Science:
- Cell Biology
- Genetics
- Metabolism
Background:
- Cell competition is a biological mechanism for eliminating less-fit cells.
- This phenomenon has been extensively studied in model organisms like Drosophila.
- Its prevalence and mechanisms in mammalian cell lines remain less understood.
Purpose of the Study:
- To investigate the occurrence and characteristics of cell competition in commonly used mammalian cell lines.
- To identify the cellular and molecular mechanisms underlying cell competition in vitro.
- To explore the role of cellular metabolism in mediating cell fitness sensing.
Main Methods:
- Utilized three standard mammalian cell lines: U2OS, 3T3, and MDCK.
- Induction of cell competition by co-culturing distinct sub-clones.
- Assessed cell death, caspase dependency, cell-cell contact requirements, and RNA synthesis.
- Analyzed cellular metabolic profiles of competing sub-clones.
Main Results:
- Stochastic sub-clones exhibiting context-dependent competitive behavior were identified.
- Cell death was observed only when winner and loser sub-clones were co-cultured.
- Cell competition and elimination were caspase-dependent and required cell-cell contact.
- The process did not require de novo RNA synthesis but involved differences in cellular metabolism.
Conclusions:
- Cell competition is a common feature of immortalized mammalian cells cultured in vitro.
- Differences in cellular metabolism are implicated as a key mechanism for sensing relative cell fitness.
- This study provides insights into the fundamental processes governing cell-cell interactions and tissue homeostasis in mammals.
