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. 2024 Jan 10;4(1):100463. doi: 10.1016/j.xgen.2023.100463

Figure 4.

Figure 4

TGF-β expression motifs are dispersed across cell types and organs

(A) We defined the dispersion of a receptor expression profile to be the within-class pairwise distance computed in a 100-dimensional PCA space constructed from the top 4,000 highly variable genes (HVGs) (left). Dispersed profiles (black) show high cell type diversity, whereas non-dispersed profiles (gray) are closer together in PCA space.

(B) The dispersion of actual TGF-β expression profiles. Dashed lines indicate the expected range (25th and 75th percentiles, respectively) of dispersions obtained by clustering similar cell types using the whole transcriptome. Note the large number of profiles with larger dispersions than expected in similar cell types.

(C) Empirical cumulative distribution functions of TGF-β profile dispersion. The observed dispersion distribution (turquoise) lies between the extremes of cell-type-specific profiles (gray) and profiles obtained by randomizing cell type distances by shuffling cell type labels (black). We classified motifs in the shaded region, defined as being in at least the 90th percentile of the related cell type dispersion distribution (gray) as motifs.

(D) We identified 14 TGF-β motifs, arranged by gene expression similarity. For each motif, the number of cell states in which it appears is indicated by the histogram at right.

(E) TGF-β motifs (rows) are broadly distributed across different tissues and organs (columns). Each matrix element represents the number of cell states in the indicated tissue or organ expressing the corresponding motif. Note that most motifs are expressed in multiple tissues or organs, and most tissues or organs contain multiple motifs.

(F) Key cell type classes, including epithelial, macrophage, fibroblast, and endothelial cell types, each span multiple TGF-β motifs. Motifs are ordered to match the ordering in (D) and (E). Each cell class mapped to multiple distinct pathway motifs yet differed in their motif diversity. For example, epithelial cells comprise a broad spectrum of 11 distinct motifs, whereas macrophages and endothelial cells are primarily restricted to smaller subsets of more closely related motifs.