Reconstruct cellular dynamics from single cell data

Recent advances of single cell techniques catalyzed quantitative studies on the dynamics of cell phenotypic transitions (CPT) emerging as a new field. However, fixed cell-based approaches have fundamental limits on revealing temporal information, and fluorescence-based live cell imaging approaches are technically challenging for multiplex long-term imaging. To tackle the challenges, we developed an integrated experimental/computational platform for reconstructing single cell phenotypic transition dynamics. Experimentally, we developed a live-cell imaging platform to record the phenotypic transition path of A549 VIM-RFP reporter cell line and unveil parallel paths of epithelial-to-mesenchymal transition (EMT). Computationally, we modified a finite temperature string method to reconstruct the reaction coordinate from the paths, and reconstruct a corresponding quasi-potential, which reveals that the EMT process resembles a barrier-less relaxation process. Our work demonstrates the necessity of extracting dynamical information of phenotypic transitions and the existence of a unified theoretical framework describing transition and relaxation dynamics in systems with and without detailed balance.