Fig. 2: Small intestinal tuft cell phenotypes are conserved between mouse and human.

a Schematic and UMAP of published single-cell transcriptomics dataset of human small intestine20. Cell types are annotated by color. EE: enteroendocrine cells. Abs. prog.: absorptive progenitors. Sec. prog.: secretory progenitors. Illustration from NIAID NIH BIOART Source bioart.niaid.nih.gov/bioart/232. b Unsupervised clustering of 844 human tuft cells20 identifies three separate tuft cell populations. c Single cell dot plot showing expression of tuft cell and proliferation markers per cluster. Average expression is represented by dot color while the percentage of expressing cells is denoted by the dot size. d Lollipop plot showing GO-term enrichment analysis (clusterProfiler; Biological Process) of human tuft-1 and tuft-2 expression profiles. Dot size represents the number of genes within the gene set, stalk length corresponds to significance (one-sided Fisher’s exact test). e Heatmap showing co-expression of tuft-1 and tuft-2 marker genes in human post-mitotic tuft cells (genes with adjusted P value < 0.01 are shown, Wilcoxon rank-sum test with Bonferroni correction). Transcriptomic profiles are ordered by their ratio of human tuft-1 and 2 signature scores, indicated at the top of the heatmap. AVIL and CHAT expression per cell is shown above the heatmap. f Zonation profile of human tuft-1 and tuft-2 populations from (b). Center of mass on crypt-villus axis22 for the top 50 cluster-specific genes is shown. Boxes in Tukey box-and-whisker plot represent interquartile range (IQR, Q1 (25th percentile) to Q3 (75th percentile)), central lines mark median values and whiskers indicate outlier boundaries (1.5*IQR) (ANOVA P = 0.002, Tukey HSD test). g Differential expression analysis between tuft-1 and tuft-2 subtypes in mouse and human (Wilcoxon rank-sum test). Tones of gray represent significance level. Tuft-specific genes, shared between human and mice, are highlighted in red. Contour plot indicates density distribution of these shared tuft-specific genes.