Extended Data Fig. 7: Obesity induces metabolic changes and downregulation of solute transporters in kidney ECs.
(a) Top 5 enriched genes in each of the kidney EC clusters. mEC – medullary ECs, gEC – glomerular ECs. (b) Obesity-associated shifts in kidney EC clusters. Populations showing a change of log2(WD/chow) > 0.5 in obesity are highlighted in color. (c) Comparison of obesity-associated gene expression changes across renal EC subtypes. Any gene showing a |log(FC)| > 0.1 in any cluster was used to collate the list of genes used for these analyses. Pearson’s r-value for each comparison is provided. (d) KEGG curated pathways significantly enriched in AP1 ECs versus other kidney ECsGenes significantly enriched (p-adj < 0.05) in AP1 ECs were used for these analyses. (e) KEGG pathways enriched in the mEC1 and mEC2 clusters relative to other kidney ECs. Genes significantly enriched (p-adj < 0.05) in mEC1 and mEC2, relative to other kidney EC populations, were used for these analyses. (f) Enrichment in the expression of metabolic genes across kidney EC clusters. Z-scores of average gene expression per cluster are presented. (g) Enrichment of genes encoding SLC transporters across kidney EC clusters. SLC transporters enriched in the mEC1 population are highlighted in red and indicated below the heatmap. (h) UMAPs showing the enrichment of Slc34a1, Slc4a4, Slc6a19, Slc5a2, Slc22a8, Slc13a1, Slc22a18 and Slc5a12 in renal mEC1 cells. The mEC1 population is marked by the black arrows. (i) Obesity-associated gene expression changes in SLC transporters in the mEC1 population. (j) Changes in the expression of mitochondrial respiratory genes in the mEC2 population in obesity. Respiratory complex identities are marked at the bottom. (k) BioPlanet curated pathways upregulated in glomerular ECs (gECs) in obesity. Top 100 downregulated genes, ranked by log(FC), were used for these analyses. (l) Top differentially expressed genes, ranked by p value, in gECs. (m) Obesity-associated changes in the expression of Notch target genes Hey1 and Hes1 in gECs. p-adj indicates adjustments for multiple comparisons using the Benjamini-Hochberg method, FC – fold change, gEC – glomerular EC, mEC – medullary EC. Differential expression from scRNA-seq data is expressed on a natural log (loge) scale.
