Figure 3 from Epigenetic Heritability of Cell Plasticity Drives Cancer Drug Resistance through a One-to-Many Genotype-to-Phenotype Paradigm

Evolutionary dynamics of barcoded population. A, Lentiviral barcode proportions following first-line treatment in MSS AKT–mutant organoid. For each replicate and drug condition, we quantified barcode proportions from genomic DNA, the only exception being trametinib, for which we used the proportion quantified from 10x scRNA-seq. The top 100 barcodes have a unique color across the whole experiment; all the others (<2% abundance) are shown in gray. All the barcodes are quantified after the regrowth period. Selection is evident when compared with the POT. B, Reconstruction of clonal dynamics using floating barcodes, extracted from culture media every 2 days over the whole length of the experiment. The dynamics show an evident clonal sweep of the blue barcode after second-line treatment with trametinib. The color code is consistent with A. Proportions are smoothed over a rolling average on a window of seven points. C, Lentiviral barcode proportions with the second-line treatment in MSS AKT–mutant organoids. D, Barcode proportions in MSI organoids after being exposed to chemotherapy (oxaliplatin) and ERK inhibition (SCH772984).