Seizure evolution in a mouse model of West syndrome involves complex and time-dependent synapse remodeling, gliosis and alterations in lipid metabolism
Fig 7
Single-nucleus transcriptomic analysis on the hippocampus of Cyfip2+/R87C mice.
(A) UMAP visualization of 12 hippocampal cell types from WT and Cyfip2+/R87C mice at PWK 28. (B) A dot plot illustrating the expression of cell-specific genes used to identify the 12 cell types, with dot size representing the percentage of cells expressing the gene and color indicating the average (Avg.) expression level. (C) Violin plot showing the expression levels of Apod and Ptgds in different cell types, grouped by genotype. (D) Subclustering results of CA1 neurons. The left panel presents a UMAP visualization of CA1 neuronal subtypes, while the middle panel features a dot plot highlighting the top DEGs for each cluster. The right panel shows the results of MiloR analysis, illustrating CA1 abundance differences, with genotypes color-coded as WT (blue) and Cyfip2+/R87C (red). (E) Heatmap displaying Over-Representation Analysis (ORA) results for regulons regulated by transcription factors (TFs) with higher activity in CA1-1 compared to CA1-0. Color intensity represents similarity, and each label corresponds to the ancestor term of the respective cluster. (F) Subclustering results of astrocytes. (G) The left panel shows a UMAP visualization of abundance analysis results, illustrating differences in astrocyte abundance between WT (blue) and Cyfip2+/R87C (red) mice. The right panel displays a volcano plot illustrating the results of the differential expression (DE) test between Astrocyte-4 and other subtypes. (H) Heatmap illustrating the ORA results for regulons governed by TFs with higher activity in Astrocyte-4 compared to Astrocyte-1. (I) Heatmap showing GSEA results for Astrocyte-4 compared to Astrocyte-1. (J) Ligand-receptor (LR) interactions between subtypes of neurons and astrocytes. Interactions were inferred from the expression profiles of ligands and receptors across different cell populations. LR interactions specific to Cyfip2+/R87C neuron-astrocyte pairs (CA1-1 to Astrocyte-4 and Astrocyte-4 to CA1-1) are highlighted in red. (K) Diagrams depicting bidirectional interactions between CA1-1 and Astrocyte-4, illustrating the potential influence of ligands on target cell gene expression (blue, downregulated; red, upregulated).