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

To enable studies of rare population of cell harboring specific point mutations, we developed STAR-FACS, Specific-To-Allele PCR-FACS. This method allows for labeling cells based on allele-specific genomic DNA in-cell amplification. Labeled cells are then sorted and profiled with bulk or single cell transcriptomics. Moreover, the protocol is also compatible with downstream characterization of chromatin features with Cleavage Under Targets and Tagmentation (CUT&Tag) method. Our proof-of-principle study shows that STAR-FACS can be used to separate cells based on TERT promoter mutation status.