Targeted DNA sequencing of barcoded SUM159PT cells

Cancer is a heterogeneous disease, where multiple, phenotypically distinct subpopulations co-exist. Tumour evolution is a result of a complex interplay of genetic and epigenetic factors. To predict the molecular drivers of distinct cancer responses, we apply single-cell lineage tracing (scRNA-Seq of barcoded cells) on a triple-negative breast cancer model. We propose GALILEO, a framework providing lineage tracing, transcriptomic, and chromatin accessibility information simultaneously at single-cell resolution (Multiome ATAC + gene expression on barcoded cells). The combination of single-cell lineage tracing with phenotypic assays allows to link a cell state with its fate. Overall design: Analysis of barcoded SUM159PT by targeted DNA-seq. Samples were collected before or after treatment with Paclitaxel (PTX), either in vitro or in vivo (transplantation into the mammary fat pad). Reference samples are called "D0". Pre-treated = cells received a first round of paclitaxel treatment before being barcoded and treated for a second round.