Figure 4.

Inflammation-associated cell states are associated with JAK/STAT signaling

(A) Heatmap of scaled transcription factor activity from the annotated DoRothEA regulons. Top three differentially active regulons for each of the cell type clusters are depicted.

(B) Heatmap of scaled pathway activity for ulcerated cell populations. Activity scores have been calculated using genes differentially expressed in the ulcerated dataset, as compared to the healthy dataset. The DEGs have been found between pseudo-bulk profiles of cell types from the two datasets when at least two biological replicates per condition were available. In the ulcerated dataset, IA Colonocytes and IA goblet cells have been combined with TA colonocytes and TA goblet cells, respectively.

(C) UMAP plot showing enrichment for STAT3 transcriptional regulon in the integrated dataset split by sample type. Arrows indicate location of IA clusters in the ulcerated samples.

(D) Venn diagram of the intersection between shared upregulated genes in IA colonocytes and IA goblet cells (compared to their respective lineages) in the ulcerated dataset.

(E and F) UMAPs with a heatmap of the normalized thirteen IA signature genes (E) and REG1A expression in as in (C).

(G) Representative immunofluorescent images for REG1A (green), TFF3 (red), and b-catenin or E-Cadherin (white) in healthy and ulcerated tissue samples. Arrowheads indicate single REG1A-positive cells. Arrows indicate TFF3/REG1A double-positive cells. Scale bars: 100 μm.