Figure 4

Analysis of the hippocampal transcriptome of Ptchd1^−/y reveals global increased expression of synaptic genes. (a) Clear segregation of wild-type (WT) and Ptchd1^−/y transcriptomes. Clustering of Pearson correlations (Ward’s linkage), an unbiased method to quantify the degree of similarity between data set, shows clear segregation between genotype and high concordance of biological replicas. (b) Upregulated genes impact the neuronal populations in the hippocampus. Radar plot representing the enrichments (hypergeometric test, Bonferroni corrected) of cell-type-specific markers³⁵ (see Supplementary Methods) in the lists of upregulated and downregulated genes. Outer rings correspond to higher enrichments (P-values represented in Z-score scale). Red and blue shape occupy largely separated areas, that is, cell types. (c) Ptchd1 inactivation is associated with the upregulation of synaptic genes. Radar plot summarizing the major gene ontology (GO) enrichments for upregulated and downregulated genes. Outer rings correspond to stronger enrichments. Bonferroni-corrected P-values are represented in Z-score scale. Upregulated genes are strongly enriched in synaptic proteins while downregulated genes seem to be implicated, among other pathways, in the mitochondrial respiratory chain and the SRP-dependent co-translational protein targeting to membrane. (d) Detailed overview on the synaptic and neurodevelopmental genes upregulated in Ptchd1^−/y hippocampi. Histogram showing the Bonferroni-corrected P-values for the selected GO enrichments. The numbers indicate the amount of genes annotated with each term in the upregulated gene set and genomewide, respectively. Almost 25% of the PSD genes are upregulated in Ptchd1^−/y hippocampi. (e) Enrichments for experimental binding sites from Cistrome chromatin immunoprecipitation-seq database. Upregulated genes are enriched in the binding sites of Suz12, Acsl1 and Rest, whereas downregulated genes are not. Complete data in Supplementary Table S9.

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