Fig. 5: Pre-existing, primed, open chromatin landscape in P5 O4+ cells, in physiological conditions (see Figs. S3, S4; see Table S5). Analysis of regions lying within ±8 kb, around the TSS of genes of the immune/inflammatory pathways (gene cluster C1) that are upregulated in O4+ cells at P5, in response to neuroinflammation.

A Multidimensional Scaling plot of distances between the 3 PBS samples and the 3 IL1B samples, of the ATAC-seq peaks associated to UP genes, using EdgeR. Distances between samples correspond to biological coefficient of variation (BCV), that represents the biological variation between neuroinflammation-exposed brains and control brains. IL1B samples are only poorly separated from PBS samples, indicating that the chromatin accessibility is mainly unchanged by neuroinflammation in the genes of the immune/inflammatory pathways in O4+ cells. B Scatter plot representing the dispersion (fold change) of peaks in relation to the number of tn5 cuts per million (logCPM), for each individual analyzed peak located ±8 kb around the TSS of UP genes after neuroinflammation, across the 3 PBS samples and 3 IL1B samples. The 27 peaks showing significant differences between IL1B and PBS conditions are indicated in red, with 22 peaks corresponding to increased (“open”) and 5 peaks to decreased (“closed”) chromatin accessibility, with FDR < 0.05, respectively. C Examples of peaks showing increased or unmodified chromatin accessibility: (Upper panel) the peaks located at the most downstream position in the Hif3a gene (Hypoxia-inducible factor 3 alpha subunit) show increased chromatin accessibility in neuroinflammation context. (Lower panel) Magnification of this region. In contrast, peaks located in the middle of the Hif3a gene show no significant changes in chromatin accessibility (see the upper panel). D Example of peak showing reduced chromatin accessibility: peaks within the Cwc22 gene (encoding the spliceosome-associated protein 22). E Examples of peaks in genes encoding cytokines and chemokines, showing no statistically relevant modification of chromatin accessibility. F Cross-species comparison confirms global similarities in the chromatin landscapes of HAEC and unstressed O4+ cell datasets. (See Table S8) Comparison of 100 peaks which were found to be differential in the HAEC (public) dataset upon IL1B treatment, among all (7739) matched peaks between human (HAEC) and mouse (O4+ cell) datasets. Reads were normalized for each set of peaks against the total number of reads present in all matched peaks and converted into reads per million. Distributions were compared using a one-sample Wilcoxon rank test.