Fig. 7: CosMx spatial transcriptomics of archived FFPE specimens with single-cell resolution identified tissue signatures of VDZ response and non-response prior to therapy in activated MNP, fibroblast, and IEC crypt base subsets.

a Schematic of retrospective, longitudinal analysis of archived FFPE specimens using 1000-plex CosMx spatial transcriptomics of 126,368 cells from 73 FOVs; n of schematic applies to left panels in (b–d). Created with BioRender.com. b, c Cell frequencies of indicated subsets comparing (left) HC and pre-treatment samples (pre-VDZ) (Mann–Whitney, two-tailed), as well as (middle, right) pre-VDZ and post-VDZ treatment for the indicated subsets for both responders (R) and non-responders (NR), only patients with matching biopsies pre- and post-VDZ are shown (Mann–Whitney, two-tailed of ∆ post VDZ - pre VDZ for R and NR). d Z-score of activated fibroblast and activated MNP neighborhood enrichment comparing (left) HC and pre-VDZ (Mann–Whitney, two-tailed) and (right) one-way ANOVA Kruskal-Wallis test with Dunn’s multiple comparison test. e Dot plot representation of a subset of genes from pseudobulk DE gene analysis for the indicated subsets. Representative spatial cell scatter plots highlighting the relevant cell subsets relatively increased in (f) VDZ R or (h) VDZ NR. Representative spatial transcript scatter plots highlighting a subset of genes relatively increased in (g) VDZ R and (i) VDZ NR. f–i Spatial scatter plots were representative of 73 FOVs. For panels (b–d), mean ± SEM; n=number of patients; each dot represents averaged FOV per patient. R-responder; NR non-responder.