Using barcodes to track cell evolution reveals drug resistance mechanisms in colorectal cancer, indicating the role of epigenetics.
Tracking evolutionary dynamics. A, Randomly expressed barcodes allow tracking of cellular evolution matched to single-cell transcriptomics. By collecting the floating barcodes in the supernatant of the culture media, we can also profile the clonal composition of the cells without perturbing them with replating. CRC, colorectal cancer. B, Heritable (genetic or epigenetic) preexisting alterations conferring resistance will show as enrichment of the same barcode in different replicas. Heritable de novo alterations may also occur during treatment rather than being preexisting; in that case, we expect enrichment for different barcodes between replicas. Finally, nonheritable mechanisms, such as plasticity, will produce drug resistance without any enrichment of barcodes. Created in BioRender. Sottoriva, A. (2025) https://BioRender.com/hu90cn3.
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