RT Journal Article
SR Electronic
T1 Live cell imaging and analysis reveal cell phenotypic transition dynamics inherently missing in snapshot data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.12.874248
DO 10.1101/2019.12.12.874248
A1 Weikang Wang
A1 Diana Douglas
A1 Jingyu Zhang
A1 Yi-Jiun Chen
A1 Ya-Yun Cheng
A1 Sangeeta Kumari
A1 Metewo Selase Enuameh
A1 Yan Dai
A1 Callen T. Wallace
A1 Simon C. Watkins
A1 Weiguo Shu
A1 Jianhua Xing
YR 2020
UL http://biorxiv.org/content/early/2020/01/27/2019.12.12.874248.abstract
AB Recent advances in single-cell techniques catalyze an emerging field of studying how cells convert from one phenotype to another, in a step-by-step process. Two grand technical challenges, however, impede further development of the field. Fixed cell-based approaches can provide genome-wide snapshots of cell status but have fundamental limits on revealing temporal information, and fluorescence-based live cell imaging approaches provide temporal information but are technically challenging for multiplex long-term imaging. We first developed a live-cell imaging platform that tracks cellular status change through combining endogenous fluorescent labeling that minimizes perturbation to cell physiology, and/or live cell imaging of high-dimensional cell morphological and texture features. With our platform and an A549 VIM-RFP EMT reporter line, live cell trajectories reveal parallel paths of epithelial-to-mesenchymal transition missing from snapshot data due to cell-cell heterogeneity. Our results emphasize the necessity of extracting dynamical information of phenotypic transitions from multiplex live cell imaging.