Spatial and temporal signatures of cell competition revealed by K-function analysis

Abstract

It is generally hypothesised that in MDCK wild-type versus ScrKD co-cultures mechanical competition leads to the physical elimination of ScrKD cells, while in MDCK wild-type versus RasV12 co-cultures biochemical competition results in the non-apoptotic extrusion of RasV12 cells. However, the exact spatiotemporal signatures of competitive interactions in these systems remains largely unknown. Utilising advanced single-cell image analysis, this research quantifies the spatiotemporal dynamics of these competitive interactions. Time-lapse microscopy, combined with cellular segmentation, tracking, cell-state classification, and K-function clustering analysis provide detailed insights into how wild-type cell proliferation relates to the elimination of mutant cells. We find striking differences in the underlying processes of each competition type. In the ScrKD competition, elimination seems driven by diffuse proliferative forces unrelated to the immediate elimination site. In contrast, RasV12 cell elimination is closely linked to local increases in wild-type cell mitoses prior to the RasV12 extrusion. Both competitions trigger an increase in local wild-type cell proliferation post-elimination, although the timing of these responses vary. This study not only sheds light on the diverse mechanisms of cell competition but also underscores the complexity of cellular interactions in tissue dynamics, providing new perspectives on cellular quality control and a new quantitative approach to characterise these interactions.