Fig. 1

a t-SNE plot of high-quality cells across all samples, colored by cell lineage. b Proportions of different cell lineages, categorized by neoadjuvant therapy strategy and colored according to cell lineage. c Heatmap shows the predicted CNVs by CopyKAT among epithelial cells across all chromosomes. The cells were clustered into two groups based on CNVs, where malignant epithelial cells had more CNVs than normal epithelial cells. d t-SNE plot of all malignant epithelial cells (Ep) in our cohort, colored by tumor cell lineages. e Proportions of tumor cell lineages in different therapy strategies. f Enriched KEGG pathways of Ep-C2 lineage based on marker genes. g t-SNE visualization of AUC scores of two regulons (TF and its target genes), split by therapy strategies. h Multiplex immunohistochemistry of pre- and post-therapy samples using the antibodies and colors are as follows: DAPI (blue), NFE2L2 (yellow), MAFG (green), OSGIN1 (Magenta), and CYP4F3 (red). i Resistance hallmarks of ESCC to neoadjuvant therapy. ECM extracellular matrix, EMT epithelial mesenchymal transition, TF transcription factor, MMPs matrix metalloproteinases, Tem effector memory T cell. j The average fractions of four types of T cell lineages under different neoadjuvant therapy. Tem effector memory T cells, Tex exhausted T cells. k Dot plot shows differentially expressed genes between Tem-GZMK and Tem-IFNG cells. l NicheNet analysis shows the potential ligands expressed by neighboring cells that presumably affected the differentially expressed genes between Tem-GZMK and Tem-IFNG cells. Ligand activity indicates the ability of each ligand to predict the target genes, and better predictive ligands are thus ranked higher. The regulatory potential score indicates the confidence that a particular ligand can regulate the expression of a particular target gene. m Violin plot shows average gene expression across all myeloid sub-populations, colored by lineage identity. Mono monocyte, Macro macrophage, DC classical dendritic cell, pDC plasmacytoid dendritic cell, pro M proliferation monocyte/macrophage. n Ligand-receptor interaction analysis between the myeloid lineage and endothelial lineage. Prior interaction potential score indicates the confidence that a particular ligand can interact with a particular receptor. o Relative interaction strength of each incoming signaling pathway among tumor cell lineages and fibroblasts in samples from chemoradiotherapy patients