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Spatial and temporal signatures of cell competition revealed by K-function analysis.
Nathan J Day1,2, Jasmine Michalowska1,2,3, Manasi Kelkar2,3
1Institute for the Physics of Living Systems, University College London, London, United Kingdom WC1E 6BT.
Molecular Biology of the Cell
|March 26, 2025
Summary
Cell competition involves mechanical and biochemical interactions. This study quantifies how winner cell proliferation differs around loser cell elimination in these two types, revealing distinct spatiotemporal patterns.
Area of Science:
- Cellular and Molecular Biology
- Developmental Biology
- Quantitative Biology
Background:
- Cell competition, a process where detrimental cells are eliminated by fitter neighbors, is crucial for tissue homeostasis and quality control.
- Existing models distinguish between mechanical competition (long-range effects) and biochemical competition (direct cell contact), but causality in spatiotemporal dynamics remains unclear.
- The roles of winner cell proliferation before and after loser cell elimination are hypothesized but difficult to experimentally verify.
Purpose of the Study:
- To quantitatively analyze and compare the spatiotemporal dynamics of winner cell proliferation surrounding loser cell elimination in mechanical and biochemical cell competition.
- To differentiate the causal relationships between proliferation and elimination events in distinct competition contexts.
- To establish a novel computational approach for characterizing cellular interactions in tissue dynamics.
Main Methods:
- Acquisition of long-term time-lapse microscopy for two models of cell competition: mechanical (ScrKD) and biochemical (RasV12).
- Advanced image analysis including cell segmentation, tracking, and precise detection of mitotic events and cell eliminations.
- Application of K-function clustering analysis to identify and quantify spatiotemporal proliferation patterns around elimination sites.
Main Results:
- Significant differences in proliferation patterns were observed between mechanical (ScrKD) and biochemical (RasV12) competition.
- In mechanical competition, proliferation was diffuse and not clustered near the elimination site.
- Biochemical competition showed clustered proliferation of wild-type cells preceding RasV12 cell extrusion, with increased proliferation post-elimination in both competition types, albeit with varying kinetics.
Conclusions:
- The study reveals distinct spatiotemporal signatures for mechanical versus biochemical cell competition, challenging uniform models of winner cell proliferation.
- Winner cell proliferation dynamics are context-dependent, occurring either diffusely or in a clustered manner preceding loser cell elimination.
- This work provides a quantitative framework for understanding cellular interactions in tissue dynamics and cellular quality control mechanisms.
