Figure 5 |. Transcriptional memory of IL-4/IL-13 exposure retained by basal cells ex vivo and in vivo IL-4Rα blockade partially resets state in polyps.
a, tSNE plot of cell types from ALI-cultures (Extended Data Fig. 9g) over 16,173 single cells (8,483 non-polyp; 7,690 polyp) and (b) violin plots for secretory genes (from Fig. 2f) on ALI secretory cells (3,277 non-polyp; 3,143 polyp); not significant (n.s.) except MUC4, PSCA and SCGB1A1 greater in polyp secretory cells; bimodal p<4.04×10−16, Bonferroni correction. c, Basal cell inflammatory memory to IL-4/IL-13 performed (Methods) and displayed as PCA over variable genes and Venn diagram overlaps of differential expression; *t-test, two-tailed, Bonferroni corrected p<0.05, Supplementary Table 3 full lists. d, CTNNB1 expression and Wnt pathway z-score (Methods) in basal cells from (c); n=4 samples/dose; 2-way ANOVA; p<0.0001 for CTNNB1; p<0.0282 for Wnt pathway, (a-d) n=2 basal cell donors each non-polyp and polyp. e-g, scRNA-seq on anti-IL-4Rα-treated individual and (e) tSNE plot of 8,764 single cells from nasal polyps colored by pre- (5,731 cells) and post- (3,033 cells) treatment samples (Extended Data Fig. 10 for more), (f) heatmap of select genes (AUC>0.68 core, p<2.46×10−5 or less with Bonferroni correction) over basal cells (200 pre, 151 post), and (g) violin plots for select genes; n.s. save *bimodal p<0.00087 with Bonferroni correction Supplementary Table 3 for full list; Wnt score Pre vs. Post: *t-test, two-tailed, p<2.2×10−16, effect size 0.942.