Cell sorting based on single nucleotide variation enables characterization of mutation-dependent transcriptome and chromatin states

Abstract

ABSTRACTSingle nucleotide variants (SNVs) contribute to cancer by altering the coding and the non-coding regions of the genome. Connecting SNVs to transcriptomic and epigenetic changes at the single-cell level remains challenging. To enable studies of rare cell populations harboring specific point mutations, we developed STAR-FACS, Specific-To-Allele PCR-FACS, to sort cells based on genomic allele alterations. We show that STAR-FACS can separate cells based on TERT promoter mutation status and is compatible with bulk and single-cell transcriptomic and epigenetic profiling. We demonstrate that glioblastoma cell lines derived from the same tumor but harboring distinct TERT promoter SNVs have different transcriptional programs.