Fig. 8: SnRNA-seq and snATAC-seq analysis of spinal cord ventral horns of 9-month-old mice.

a Cell clustering of integrated snRNA-seq data visualized by t-SNE plot. Clusters were grouped and annotated according to the expression of marker genes. b Heatmap describing marker genes enriched in 5 cell types. c GO of significant DEGs in neuron, determined by Wilcoxon test, were selected for GO analysis. Upregulated genes in Mut mouse (top), downregulated genes (bottom). d PPI analysis of proteins interact with PCDHA9 (circle) and their predicted associated proteins (diamond), that are also encoded by genes associated with significant DARs in snATAC-seq. Colors represent different GO terms. Proteins marked in red are also DEGs (Hspa8, Lsamp and Actb), TF Rxra is marked in purple and Fxyd2 that interacts with NKA-α1 is marked in blue. Network was generated by STRING tool. e GRN generated based on integration of snRNA-seq and snATAC-seq. f Malat1 was predicted to modulate the 35 upregulated genes in snRNA-seq neuron cluster (the outermost ring) through miRNAs (the middle ring). The miRNAs marked with pink color represent neuron axon-localized miRNAs and the genes in the outermost ring marked with purple are degenerative diseases associated genes and the one related to Fyn (Plekhg1). g Heatmap depicting the total normalized number of ligand-receptor interactions between cell types in WT and Mut snRNA-seq data obtained with CellPhoneDB v.3.0. h Potential neurodegeneration diseases associated ligand-receptor pairs linking neuron to other cell types shown as scaled mean, as calculated by CellphoneDB. The analysis was based on significance level of p < 0.5. Short name in (g, h): (OL: oligodendrocyte. N: neuron. A: astrocyte. M: microglia. OP: oligodendrocyte progenitor cell). i Schematic diagram of the mechanism by which mutations in PCDHA9 lead to ALS. Source data are provided as a source data file.