Fig. 4: NiCo infers cell state covariation between mouse intestinal stem cells and Paneth cell progenitors.

a Spatial representation of cell type annotations obtained with NiCo. See legend in (b). b UMAP representation based on gene expression of the spatial data. Cell type annotations obtained with NiCo are highlighted. The legend indicates the number of cells for each cell type. cDC, conventional dendritic cell; pDC, plasmacytoid dendritic cell. c Confusion matrix highlighting predictive capacity of the niche for all cell types. d Regression coefficients reflecting local niche interactions for stem/TA cells (top) and Paneth cells (bottom). Regression coefficients (y-axis) were ordered by decreasing magnitude (x-axis). The red dotted line indicates the threshold for cell type interaction (c = 0.1) applied in (e). Error bars, see “Methods”. e Cell type interaction map derived from the regression coefficients of NiCo’s interaction module (Methods). Arrows point from predictive niche cell types towards the central cell type. f, Covariation between stem/TA factors (y-axis) and co-localized neighborhood cell type factors (x-axis). Circle size scales linearly with -log₁₀(p-value), and circle color indicates ridge regression coefficients. S denotes the normalized niche coefficient score. The multivariate regression p-value was derived from two-tailed t-statistics. g Spearman correlations (left) and average expression (right) for the top 20 positively correlated genes from scRNA-seq reference data for stem/TA Fa1 and Paneth Fa1. Dashed line demarcates the genes associated with each cell type. h Ligand-receptor pairs correlated with stem/TA cell Fa1 and Paneth cell Fa1 (cc, central cell; nc, niche cell). The rectangle’s north and south faces represent ligand and receptor correlation to the factors, while west and east faces represent the proportion of ligand and receptor expressing cells. Ligands, y-axis; receptors, x-axis. See “Methods”. i UMAP visualization of intestinal cell types (left) and normalized expression of Wnt3 (center) and Fzd7 (right). Data from Böttcher et al.⁵³. Cell counts are indicated in the legend.