Fig. 4.

Loss of Fkbp5 leads to cell-specific and sex-dependent molecular profiles that are highly region distinctive. (A) A large differential expression profile could be found within the BNST of female Fkbp5^Dlx mice and the DHC of male Fkbp5^Dlx older aged mice. (B) These regulated transcriptional profiles were unique for Fkbp5^Dlx vs. Fkbp5^Nex mice. (C) Within the BNST of Fkbp5^Dlx female mice, the top significantly DEGs consisted of up- and downregulated genes, whereas the top DEGs for the DHC of Fkbp5^Dlx male mice only included downregulated genes. (D) GO-enrichment analyses revealed enriched biological processes, cellular components and molecular functions in samples of our two separate transcription profiles. For the BNST of Fkbp5^Dlx female mice, regulated genes were particularly related to immune functions. Regulated genes of the DHC of Fkbp5^Dlx male mice were on the other hand predominantly associated with metabolic processes and ribosomal structural and functional mechanisms. Using a VHC single-cell sequencing dataset (E), we found that significant DEGs in the BNST of Fkbp5^Dlx female mice are highly enriched in microglia.