Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing

Abstract

Significance Tumor cells are heterogeneous, and much variation occurs at the single-cell level, which may contribute to therapeutic response. Here, we studied drug resistance dynamics in a model of tolerance with a metastatic breast cancer cell line by leveraging the power of single-cell RNA-Seq technology. Drug-tolerant cells within a single clone rapidly express high cell-to-cell transcript variability, with a gene expression profile similar to untreated cells, and the population reacquires paclitaxel sensitivity. Our gene expression and single nucleotide variants analyses suggest that equivalent phenotypes are achieved without relying on a unique molecular event or fixed transcriptional programs. Thus, transcriptional heterogeneity might ensure survival of cancer cells with equivalent combinations of gene expression programs and/or single nucleotide variants.

Keywords

Affiliated Institutions

• Dovetail Genomics (United States) US
• Salk Institute for Biological Studies US
• University of California, Santa Cruz US

Related Publications