Extended Data Fig. 4: scATAC+RNA-seq identifies DORCs and gene regulatory networks in CAR T cells.

a, Peak-gene links are identified with scATAC+RNA-seq data in Figs. 2 and 3. The number of peak-gene links plotted against the distance to linked gene TSS in CD8⁺ CAR T cells from mice inoculated with E2A-PBX1 (left) or B16-CD19 (right). b, The distribution of the number of peaks linked to each gene (left) or the number of genes linked to each peak (right) as in a. c, Genomic loci of two representative DORCs, Nr4a1 and Tox, in CD8⁺ CAR T cells against B16-CD19. Chromatin accessibility and mRNA level (violin plots) of indicated genes in each CAR T cell subset defined by scATAC-seq as in Fig. 3a are shown. d,e, Heatmaps illustrating the expression of DORC-associated genes in each subset identified in CD8⁺ CAR T cells against E2A-PBX1 (d) as in Extended Data Fig. 2b or B16-CD19 (e) as in Extended Data Fig. 3a. f, g, Scatter plots showing all association between transcription factors and DORC-associated genes in CD8⁺ CAR T cells against E2A-PBX1 (f) or B16-CD19 (g) defined in Fig. 4a. For each transcription factor-DORC pair, transcription factor motif enrichment in the DORC is plotted against the correlation between the mRNA level of the enriched transcription factor and the chromatin accessibility of the DORC. h, Transcription factors with regulation score >1 in CD8⁺ CAR T cells from mice inoculated with E2A-PBX1 or B16-CD19. i,j, Gene regulatory networks in CD8⁺ CAR T cells from mice inoculated with E2A-PBX1 (i) or B16-CD19 (j) are constructed using transcription factor to DORC-containing gene associations. k, Gene regulatory network in the T_ex-like subset from B16-CD19. l, Enrichment of hub transcription factors from the T_s-like subset, T_eff-like subset or T_ex-like subset in the TCF7 regulon in B cell ALL patients treated with CD19 CAR T cells²³. One-sided Fisher’s exact test was used to calculate the P Value.