RT Journal Article
SR Electronic
T1 Large-Scale Analysis of Cell Death Phenotypic Heterogeneity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.28.970079
DO 10.1101/2020.02.28.970079
A1 Zintis Inde
A1 Giovanni C. Forcina
A1 Kyle Denton
A1 Scott J. Dixon
YR 2020
UL http://biorxiv.org/content/early/2020/02/29/2020.02.28.970079.abstract
AB Individual cancer cells within a population can exhibit substantial phenotypic heterogeneity such that exposure to a lethal agent will kill only a fraction of cells at a given time. Whether common molecular mechanisms govern this fractional killing in response to different lethal stimuli is poorly understood. In part, this is because it is difficult to compare fractional killing between conditions using existing approaches. Here, we show that fractional killing can be quantified and compared for hundreds of populations in parallel using high-throughput time-lapse imaging. We find that fractional killing is highly variable between lethal agents and between cell lines. At the molecular level, we find that the antiapoptotic protein MCL1 is an important determinant of fractional killing in response to mitogen activated protein kinase (MAPK) pathway inhibitors but not other lethal stimuli. These studies lay the foundation for the large-scale, quantitative analysis of cell death phenotypic heterogeneity.