Fig. 6

Repeated reminder shock and a high-fat diet (HFD) induced differential changes in the ventromedial hypothalamus (VMH) of male and female mice. (A) Illustration outlining the snRNA-seq procedure utilizing the 10X Genomics platform workflow, which involves isolating nuclei from the VMH of male and female mice fed a HFD (n = 5 pooled). (B) UMAP plot displaying single cells from this study, color coded by cell type, with cell types identified based on the expression of canonical marker genes. (C) UMAP plot of single cells from the VMH cohort, color coded by cell type and segregated by sample. (D) Heatmap depicting the relative fractions of each cell type in each sample. (E) Heatmap illustrating the regulon activity of the indicated transcription factors, indicating the intensity of gene regulation in specific cell types from the VMH of males and females. (F) UMAP plot of the indicated cell types from the VMH cohort separated by sample; adjacent violin plots displaying the expression levels of specific genes are shown. G, H & I. Volcano plot illustrating differentially expressed genes (DEGs) with fold changes plotted against p values; female vs. male in microglia (G), male vs. female in astrocytes (H), and female vs. male in oligodendrocytes (I). Violin plots highlighting the highly upregulated genes. J, K & L. Pathway analysis of DEGs showing neuroinflammation (J), astrocyte activation (K), and microglial activation (L). M. Interactome representation based on DEGs from male and female mice indicating the strength of interaction between specific cell types. N. Heatmap exhibiting the indicated ligand-cell interactions in male and female mice