Uncovering the behaviors of individual cells within a multicellular microvascular community

Abstract

Although individual cells vary in behavior during the formation of tissues, the nature of such variations are largely uncharacterized. Here, we tracked the morphologies and motilities of ∼300 human endothelial cells from an initial dispersed state to the formation of capillary-like structures, distilling the dynamics of tissue morphogenesis into an array of ∼36,000 numerical phenotypes. Quantitative analysis of population averages revealed two previously unidentified phases in which the cells spread before forming connections with neighboring cells and where the microvascular plexus stabilized before spatially reorganizing. Analysis at the single-cell level showed that in contrast to the population-averaged behavior, most cells followed distinct temporal patterns that were not reflected in the bulk average. Interestingly, some of these behavioral patterns correlated to the cells' final structural role within the plexus. Knowledge of how individual cells or groups of cells behave enhances our understanding of hownative tissues self-organize and could ultimately enable more precise approaches for engineering tissues and synthesizing multicellular communities.