Single-cell approaches to cell competition: high-throughput imaging, machine learning and simulations

TL;DR

This review discusses advanced single-cell analysis techniques, including high-throughput imaging, machine learning, and simulations, to understand the mechanisms and dynamics of cell competition in tissues.

Contribution

It introduces quantitative metrics and experimental strategies for analyzing single-cell behaviors in tissue competition, integrating imaging, machine learning, and computational modeling.

Findings

Quantitative metrics distinguish types and outcomes of cell competition.

High-throughput imaging combined with machine learning enables detailed single-cell analysis.

Computational models incorporating mechanical interactions and decision rules elucidate competition mechanisms.

Abstract

Cell competition is a quality control mechanism in tissues that results in the elimination of less fit cells. Over the past decade, the phenomenon of cell competition has been identified in many physiological and pathological contexts, driven either by biochemical signaling or by mechanical forces within the tissue. In both cases, competition has generally been characterized based on the elimination of loser cells at the population level, but significantly less attention has been focused on determining how single-cell dynamics and interactions regulate population-wide changes. In this review, we describe quantitative strategies and outline the outstanding challenges in understanding the single cell rules governing tissue-scale competition dynamics. We propose quantitative metrics to characterize single cell behaviors in competition and use them to distinguish the types and outcomes of competition. We describe how such metrics can be measured experimentally using a novel combination of high-throughput imaging and machine learning algorithms. We outline the experimental challenges to quantify cell fate dynamics with high-statistical precision, and describe the utility of computational modeling in testing hypotheses not easily accessible in experiments. In particular, cell-based modeling approaches that combine mechanical interaction of cells with decision-making rules for cell fate choices provide a powerful framework to understand and reverse-engineer the diverse rules of cell competition.