Extended Data Fig. 7: Immune-interacting fibroblasts cluster into two functionally distinct groups.
FiNi-seq and control cells were obtained from young and old livers and sequenced with FiNi-seq and conventional scRNA-seq, respectively. a, Expression of Wnt ligand genes and Wnt receptor genes by whole dataset. b, Chord diagram showing the Wnt and non-canonical Wnt (ncWnt) signaling pathways between the FiNi-seq enriched cell types and the fibroblast subtypes. c, UMAP projection of the Axin2 expression in the fibroblasts in the whole dataset. d, Volcano plot showing the DEGs between FB_Wif1 and FB_Smoc1 (two-sided t-test). e, Top gene-ontology terms for the FB_Wif1 and FB_Smoc1 cells. P-value calculated by Fisher’s exact test with Benjamini-Hochberg correction. f, The GSE137720 scRNA-seq dataset shows the liver cells at multiple time points after CCl4-mediated induction of liver fibrosis. The figures show UMAP projection of the vascular smooth muscle cells (VSMCs), fibroblasts (FB), and hepatic stellate cells (HSCs) (left) and the liver cells in the untreated and the CCl4-treated mice at 72 hours and 6 weeks (right). g, Liver portal injury was induced in young mice by feeding them 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 6 weeks. Sirius-Red staining revealed fibrosis in the portal area at 6 weeks. h, RNAscope assay showing the FB_Smoc1 marker Fmod (left), the Fibrotic EC marker Sema3g (right), and the senescence marker Cdkn1a (left and right) in control samples. i, Scatter plot showing the expression of Wif1 and Smoc1 with human age with regression line. The data are presented as mean ± 95% c.i. The correlation coefficients and p-values were calculated with two-sided Pearson’s correlation test. p = 0.139 (FB_Wif1), p = 9.136×10−27 (FB_Smoc1). j-l, The GSE261088101 scRNA-seq data shows liver cells at multiple time points in MASH model. j, (Left) UMAP of all data with fibroblast population highlighted. (Right) UMAP projection of fibroblast subtype markers. k, (Left) UMAP projection showing fibroblast subtypes (top) and conditions (bottom). (Right) Bar plot showing proportion of fibroblast subtypes by condition. l, Dot plot showing expression of fibroblast-characterizing genes within fibroblast subtypes, categorized by both condition and age. CCl4, carbon tetrachloride. DEG, differentially expressed genes.
