Extended Data Fig. 3: Cellular memory following chronic colitis.

a, Gene ontology for genes upregulated in stem cells at acute or chronic injury. b, Schematic for computing neighborhood enrichment by sample. c, scATAC-seq UMAP embedding showing enrichment for each colitis stage in k-NN networks, with each point representing a single cell colored by the enrichment of its k-NN network for a given stage. d, scRNA-seq UMAP embedding showing enrichment for each colitis stage in k-NN networks, with each point representing a single cell colored by the enrichment of its k-NN network for a given stage. e, Change in motif accessibility in stem cells at each stage of colitis. The size of the circle represents the -log10(FDR) and the color represents the magnitude of change in motif score. f, Left, change in mean motif accessibility relative to controls across colitis progression in differentiated epithelial cells. Right, barplot demonstrating change relative to control in motif accessibility, where each point represents mean change across all cells of that type within each animal. n = 9 control, 4 acute, 5 chronic and 5 recovered mice. g, Single cell motif accessibility for select motif families. n = 500 cells across all animals at each stage. P-value from two-sided Wilcoxon rank-sum test. h, Top, AP-1 motif accessibility scores plotted on stem/progenitor UMAP re-embedding. Bottom, identification of high AP-1 cells (motif score > 1.5) identified in Fig. 1. i, Differential gene expression between high AP-1 cells and all others. The X-axis represents log2(fold change) between AP-1 high cells and all others, and the Y-axis represents FDR following two-sided Wilcoxon rank sum test. j, Differential motif accessibility between high AP-1 cells and all others. The X-axis represents change in motif score between AP-1 high cells and all others, and the Y-axis represents FDR following two-sided Wilcoxon rank sum test. k, Violin plots of single cell motif accessibility values for AP-1 high and all other stem/progenitor cells. l, Change in Fos+ percentage across extended recovery, where each point represents one animal. control n = 3, acute n = 2, chronic n = 2, early recovery n = 3, 50-day recovery n = 3, 79-day recovery n = 2, and 102-day recovery n = 4 mice. m, Change in AP-1 motif accessibility across extended recovery, where each point represents average across all cells belonging to one animal. control n = 14, acute n = 4, chronic n = 5, early recovery n = 5, 50-day recovery n = 2, 79-day recovery n = 2, 102-day recovery n = 4 mice. All error bars are s.e.m.