Fig. 4: Both ECS and Fluoxetine drive transcriptomic shifts, indicating greater neuroplasticity and a more prominent immature phenotype among granule neurons.

A Single-nucleus RNA sequencing was performed on hippocampal nuclei from four treatment groups: vehicle (Veh), corticosterone (Cort), Cort plus fluoxetine (Flx), and Cort plus 10x ECS (N = 3 per group). Neuronal nuclei were identified with the NeuN antibody, followed by cell sorting. UMAP clustering of all neurons revealed a granule neuron population that was used for all subsequent analyses. B UMAP projections of the granule neuron population, labeled by treatment condition. C Genes identified in Hochgerner et al 2018 as those predominantly expressed in either mature or immature cell types were used to produce mature vs immature phenotype module scores. UMAP projections depict granule neurons from all treatment conditions, while color encodes the intensity of expression of mature vs immature module scores. D Mature vs immature phenotype module score was used to identify mature vs immature cell clusters. UMAP clustering of mature (red) and immature (blue) nuclei by treatment condition is depicted. E The percent of granule neurons in the immature cell cluster is greater for Flx and ECS-treated mice vs Cort alone. Each point represents a single mouse (One-way ANOVA with Tukey post hoc, * p ≤ 0.05, ** p ≤ 0.01).