Fig. 1

Barcode lineage tracing identifies alternative modes of drug resistance in patient-derived gliomaspheres. a Schematic depicts models of drug resistance involving outgrowth of fit genetic subclones or broadly induced cell state transitions that confer tolerance. b Schematic depicts lineage barcoding strategy wherein cells are lentivirally transduced with a unique barcode that is transcribed, enabling its identification by gDNA sequencing or scRNA-seq. c Experiment #1 design notates four replicates of GSC8 cells treated with the PDGFRA inhibitor dasatinib and the timepoints at which barcode abundances were analyzed by gDNA sequencing. d Barplots depict relative abundances of the top 20 lineages in each Experiment #1 replicate after 70 days of dasatinib treatment, per gDNA sequencing. The barcode ID of the dominant lineage in each replicate is indicated. e Dotplots depict relative abundances of indicated barcode lineages at successive timepoints in the different Experiment #1 replicates. Each plot shows data for a different lineage barcode that corresponds to the top lineage identified at day 70 in one of the replicates (see panel d). The data show that each jackpot lineage was specific to one replicate. f–h Similar representation as in panels c–e for six replicates of Experiment #2. The data indicate that a single “jackpot” lineage (e86vac) outgrew in all replicates in Experiment #2, including at earlier timepoints