Figure 1. Sex differences in immune modulation of microglial developmental programs.
(a) Hippocampal microglia isolated from male and female mice at different developmental time points were subjected to RNA extraction and Next Generation sequencing. (b) A total of 4645 genes were found to be down-regulated over development whereas 3038 genes were up-regulated from E18 to P60 in mouse microglia. (c) Developmental indices were created by taking the ratio of the average scaled expression levels of genes that were up-regulated during development in microglia, divided by the average expression levels of all down-regulated genes. (d) Line graph plots microglia index (MDI) across development against log2 age in weeks post conception (Non-linear fit, MDI R2 = 0.8525). (e) In order to validate the robustness of the index, gene group size was progressively increased 2-fold from 2 to 256 up- and down-regulated genes. (f) MDI was calculated from transcriptome data of mouse male and female microglia obtained from different developmental time points (E18, P4, P4 and P60, n = 4–10 per group, two-way ANOVA, post-hoc * p < 0.05). (g) Log fold-changes in gene expression between males and females at P60 were compared to those of P60vsE18 (developmental gene expression changes) to obtain positive correlation (Linear regression, Pearson’s r = 0.3311, *** p < 0.0001).