Fig. 4: Enrichment of the LA cell signature by spatial transcriptomics analysis is diminished in inflammation.
a, Schematic of the setup and analysis of the spatial transcriptomic experiment. b, Top, relative abundance of LA in Hh-infected mice versus Hh/anti-IL10R mice by NMF analysis (top) and manual annotation (bottom). c, H&E staining of Hh-infected tissue. Localization of LA-associated factor 15 by NMF decomposition as defined in Extended Data Fig. 8c (top left) and manual annotation (top centre and right) in the Visium RNA capture spots of a representative sample. Localization and normalized cell-type abundance of eMBCs (bottom left), naive CD8+ T cells (bottom middle) and LTi-like ILC3s (bottom right) in a representative LA. Scale bars, 200 μm. d, Cell-state enrichment ordered by cell lineage in the manually annotated LA versus LP spots in Hh-infected (top) and Hh/anti-IL10R (bottom) mice. Statistically significant enrichments (chi-square test, adjusted P value (Padj) < 0.05) are shown in magenta. Data are log2OR value ± s.d. progen. progenitor; TA, transit amplifying; GC, germinal centre; GC.BC/DZ-pre-mem, germinal centre B cell/dark zone and pre-memory; PC, plasma cell. e, CD11c and SIRPα immunofluorescence and DAPI staining in Hh/anti-IL10R mice, showing LA and surrounding LP. Scale bar, 100 μm. f, CD206 immunofluorescence and DAPI staining in Hh/anti-IL10R mice, showing LA and surrounding LP. Scale bar, 100 μm. g, Density of CD11c+SIRPα+ dendritic cells and CD206+ macrophages in LA and LP of Hh/anti-IL10R mice. h, Ratio of SIRPα+ dendritic cell and CD206 macrophage cell densities in LA vs LP in Hh and Hh/anti-IL10R mice. a–d,i, Four individual mice per group sequenced from two Visium slides. e–h, Two independent experiments with n = 6 per group. Each dot represents one mouse. g,h, One-way ANOVA using Tukey’s multiple comparisons test with single pooled variance.
