Spike-in normalization for single-cell RNA-seq reveals dynamic global transcriptional activity mediating anticancer drug response.

ABSTRACT: The transcriptional plasticity of cancer cells promotes intercellular heterogeneity in response to anticancer drugs and facilitates the generation of subpopulation surviving cells. Characterizing single-cell transcriptional heterogeneity after drug treatments can provide mechanistic insights into drug efficacy. Here, we used single-cell RNA-seq to examine transcriptomic profiles of cancer cells treated with paclitaxel, celecoxib and the combination of the two drugs. By normalizing the expression of endogenous genes to spike-in molecules, we found that cellular mRNA abundance shows dynamic regulation after drug treatment. Using a random forest model, we identified gene signatures classifying single cells into three states: transcriptional repression, amplification and control-like. Treatmen

SUBMITTER: Wang X 

PROVIDER: S-EPMC8210883 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature