Figure 1.

Single‐cell analysis of gastric cancer patient‐derived cells reveals 5‐fluorouracil (5‐FU)‐mediated alteration of cell heterogeneity and outlier cells. A, Schematic diagram of lineages in gastric normal tissue. The gastric cells shown on the top are differentiated, while the cells on the bottom of the schematic are undifferentiated. Representative markers of each cell used in the single‐cell analysis are indicated. B, Identification of the persister‐related genes. Cells were treated with the indicated drugs and subjected to GeneChip microarray analysis. Values indicate the fold induction of the gene in the drug‐treated persister cells. C, Hierarchical clustering of the single‐cell gene expression data in JSC15‐3 cells untreated or treated with 5‐FU based on the gene list in Table S3. Vertical axis: gene. Horizontal axis: cell. Green line and pink line indicate the untreated cells and 5‐FU‐treated cells, respectively. D, t‐Distributed stochastic neighbor embedding (tSNE) analysis with the single‐cell analysis data in (C). Red, light green, blue and brown indicate the untreated cells, the untreated cells in 5‐FU‐treated cells clusters, 5‐FU‐treated cells and 5‐FU‐treated cells in untreated cell clusters, respectively. In (C) and (D), the cells were treated with 5‐FU for 7 days followed by an additional 4 days without the drug to minimize the contribution of transient drug‐induced gene expression