Fig. 5: Lithium’s effect on the expression of genes in hippocampal progenitors and its overlap with genes regulating the volume of the dentate gyrus.
a The anatomy of the hippocampus, including the dentate gyrus where adult neurogenesis occurs. b A bar chart illustrating the results from our gene-set enrichment analyses. Gene sets comprise of upregulated and downregulated genes (PFDR < 0.05) in response to the high lithium dose. These sets of genes were tested for overlap with those implicated in the regulation of whole hippocampal volume and the volume of dentate gyrus (DG) subfields where neurogenesis takes place. Stronger significance is indicated by a larger bar, and -log(p) value. The dashed line represents the nominal significance threshold (p = 0.05). The overlap between genes upregulated in response to lithium and those regulating the size of the molecular cell layer of the dentate gyrus was the only test that remained significant after multiple testing correction (PFDR < 0.1). c A gene network image generated using GeneMANIA. This describes genes significantly affected by lithium in our hippocampal progenitor cell model (PFDR < 0.05), which were also associated with volume in the molecular layer based on gene-level enrichment analyses (P < 0.05). Lines represent expected interactions between genes (orange = predicted interactions, purple = interactions based on co-expression, pink = physical interactions, blue = interactions based on colocalization, green = genetic interactions, yellow = shared protein domains). Genes input into GeneMANIA are represented by circles with diagonal lines, genes hypothetically interacting within this network are represented by solid circles. LAMC1 interacted with the most genes relative to other genes input into GeneMANIA, suggesting it might represent an important hub gene.
