Figure 3
Single-cell spatial mapping of spatial transcriptomic data using matched snRNAseq data enables the creation of a spatially resolved, single-cell transcriptomic atlas with 24 discrete liver cell phenotypes. (A) Paired snRNAseq data were generated for each Visium sample (normal liver and BA liver with advanced fibrosis). UMAP visualization of single cells clusters by sample after cell labelling using established markers. (B) Gene expression heatmap of individual cell types with corresponding cell-type markers. (C) Spatial visualization of single-cell spatial mapped dataset. The left column represents the tissue slide after H&E principal staining and the right column includes overlay of single cell types after single-cell spatial mapping. The regions with absent cells represent regions with no spatial spots as they were discarded due to poor quality during our quality control steps. (D) Cell proportion comparison between normal and BA with advanced fibrosis using permutation testing (red signifies FDR < 0.05 and abs(Log2(Fold Change)) > 0.58). BA liver with advanced fibrosis has higher proportions of cholangiocytes, LSEC zone 1, T/NK cells, B/plasma cells, IZ 3, HSC/Fibroblasts, and portal endothelial cells. Normal liver has higher proportions of endothelial progenitor cells, LSEC zones 2&3 1, hepatocyte progenitor cells, PP 3 cells, and CV 2 cells. (E) Correlation plots of cell clusters for both normal and BA with advanced fibrosis samples using single-cell spatially mapped data. Line thickness correlates to spatial associations between two cell types. Overall, strength of spatial association is decreased in BA with advanced fibrosis. When looking closer at the individual interactions, BA with advanced fibrosis sees an increase in the strength between endothelial cells, immune cells, and between HSC/Fibroblasts with B/Plasma cells and cholangiocytes. CV central-venous hepatocytes, HSC hepatic stellate cells, IZ interzonal hepatocytes, LSEC liver sinusoidal endothelial cells, NK natural killer cells, PP periportal hepatocytes. All figures were created in R (version 4.2.2).
