Fig. 5: Heterogeneity of hepatocytes and its role in lactation.
a, UMAP plot of ten hepatocytes subtypes (HPE0–9), with cells color-coded according to subtype. b, Bubble plot displaying the standardized expression of the marker genes of each cell subtype. c, Pearson correlation of hepatocyte subtypes between cattle, humans and mice, calculated based on 92 spatial localization marker genes in human and mouse hepatocytes. A two-sided Wilcoxon rank-sum test was used. *Padj < 0.05, **Padj < 0.01, ***Padj < 0.001. d, Heatmap showing the GO terms and KEGG pathways of upregulated DEGs from each hepatocyte subtype using single-sample gene set variation analysis. e, UMAP plot displaying key cell types identified using GWAS enrichment analysis with scPagwas, integrating GWAS data with MY, FY and PY. The P value was calculated using a two-sided hypergeometric test, adjusted using multiple comparisons (FDR). f, GSEA of GO terms was performed using the fgsea package. Genes were ranked according to the log2(fold change) of DEGs in HPE2; a one-sided permutation test with 10,000 iterations was used to calculate the P values. g, UMAP plot depicting the developmental trajectory of hepatocyte subtypes over a pseudotime series. h, Heatmap showing the changes in gene expression of representative DEGs (q < 1 × 10−4) in the pseudotime series, and GO enrichment analysis of DEGs reclustered into two clusters (bottom left). i, Volcano plot illustrating the DEGs between cattle and human hepatocytes. j, GO terms of DEGs between cattle and human hepatocytes. The P value was calculated using a one-sided hypergeometric test and adjusted for multiple comparisons (FDR). ECM, extracellular matrix; NES, normalized enrichment score; TGFβ, transforming growth factor beta.
