Extended Data Fig. 4: Liver ECs activate lipid mobilization networks in obesity.
(a) Top 5 enriched genes in liver EC clusters. (b) Comparison of obesity-associated gene expression changes across EC clusters in liver. Any gene showing a |log(FC)| > 0.1 in any cluster was used to collate the list of genes used for these analyses. The numbers show the Pearson’s r-value for each comparison. (c) BioPlanet-annotated pathways significantly enriched in the liver cap1 population relative to other capillary ECs. Data are expressed as -log10(p-adj). (d) BioPlanet-annotated pathways significantly enriched in the liver cap2 population relative to other capillary ECs. Data are expressed as -log10(p-adj). (e) KEGG and BioPlanet terms most significantly enriched in cap2 versus cap1 population. Data are expressed as -log10(p-adj). Genes significantly enriched (p-adj < 0.05) in the cap2 population versus cap1 were used for this analysis. (f) UMAPs showing expression of Apoa1, Apoa2, Apoc1, Alb, Apoe and Abca1 in ECs across all organs. (g) Heatmap showing induction of lipid mobilization genes in liver EC clusters relative to chow controls. (h-i) Induction of (h) Fabp4 and (i) Fabp5 mRNA expression in response to 100 µM, 400 µM and 800 µM free fatty acids (FA), as well as 30 mM glucose and 10 µg per ml insulin in primary mouse liver and lung ECs. Data were standardized against BSA-treated controls and are presented as mean ± SEM. N = 4 replicates per group, with ECs for each replicate derived from a different animal. Expression data were standardized to Gapdh and Rplp0. (h) **p = 0.002; (i) ***p = 0.0003, *p = 0.021 (two-sided Student’s t-test). Each condition was compared against BSA-controls. (j) KEGG, BioPlanet and gene ontology – biological process (GO BP) terms enriched in genes downregulated in the liver cap1 population in obesity. Data are expressed as -log10(p-adj). p-adj indicates adjustments for multiple comparisons using the Benjamini-Hochberg method, FC – fold change. Differential expression from scRNA-seq data is expressed on a natural log (loge) scale.
