Fig. 1

Barcode-based tracing of cell lineages in HCC xenografts and identification of sorafenib-resistant lineages. (A) Schematic of the experimental procedure for barcode lineage tracing and single-cell RNA sequencing (scRNA-seq). (B) Venn diagram of the numbers of barcodes identified in replicates of DN and DT. DN, drug-naive tumors (n = 2 mice); DT, drug-treated tumors (n = 4 mice). (C) Venn diagram of the numbers of unique barcodes identified in the two types of tumors. (D) Differences in the frequencies of the 2,539 barcodes from panel C between sorafenib-treated and drug-naive tumors. (E and I) Cell clusters from drug-naive and drug-treated tumors based on uniform manifold approximation and projection (UMAP) of scRNA-seq data. (F and J) UMAP visualization of tumor cells expressing the 1,241 barcodes (termed barcodehigh in panel D) (blue dots), and cells without those barcodes (gray dots). (G and K) Proportions of cells that expressed a barcodehigh in each cluster from panels E and I. (H and L) The trend of proportion of cells with a barcodehigh ranging from 0 to 1,241 in each cluster of DN and DT