Fig. 2: The overall physiological and dynamic expression of genes of the immune system and inflammatory response is perturbed by neuroinflammation (See also Table S1). Microarray analysis comparing gene expression in isolated O4+ cells from six independent control (PBS) and six independent neuroinflammation-exposed cortices (IL1B; see Fig. 1). | Cell Death & Disease

Fig. 2: The overall physiological and dynamic expression of genes of the immune system and inflammatory response is perturbed by neuroinflammation (See also Table S1). Microarray analysis comparing gene expression in isolated O4+ cells from six independent control (PBS) and six independent neuroinflammation-exposed cortices (IL1B; see Fig. 1).

From: Epigenetic priming of immune/inflammatory pathways activation and abnormal activity of cell cycle pathway in a perinatal model of white matter injury

Fig. 2

A Major transcriptomic activation of the immune/inflammatory pathways in O4+ cells (cluster C1) by neuroinflammation, concomitant to alteration of cell cycle (cluster C2), myelination gene (cluster C3), and angiogenesis (Cluster C4) gene expression programs. (Left) Heat map of genes showing dynamic changes of expression between P5 and P10 in response to neuroinflammation. A fold-change (FC) threshold of ±1.5 was chosen, with FDR < 0.05. The heat map is centered around the median of the 6 values, with the color scale: log2 [−1.0; +1.0]. Transcriptomic analysis reveals 4 groups of genes with distinct expression profiles (clusters C1 to C4). Hierarchical clustering, rows, one minus Pearson correlation, linkage method: average. (Right) Total numbers of probes and corresponding genes belonging to clusters C1 to C4. B The top5 GO-terms of upregulated genes in P5 O4+ cells correspond to immune system and inflammatory response pathways. C Constitutive expression of genes encoding cytokines and chemokines at early stages of normal (unstressed) O4+ OPC maturation. RT-qPCR analyses in P3, P5, and P10 isolated O4+ cells. N = 5–6 independent experiments. Two-way ANOVA followed by Bonferroni - Post Hoc Test was performed: * and +p < 0.05; ** and, ++p < 0.01; ***p < 0.001. *, **, or ***, correspond to comparison between PBS and IL1 conditions for a given postnatal stage; + (or++), correspond to comparison between P5 (or P10) to P3. Myelination genes are plotted as a control of the effect of neuroinflammation on O4+ cells at P10. Note that in this set of experiments the downregulation of myelination genes by neuroinflammation was not observed at P5, a stage at which these genes only start to be expressed. D O4+ cells from naïve pups also constitutively express cytokine and chemokine genes. RT-qPCR experiments comparing O4+ cells from naïve (no injection), PBS-injected and IL1B-injected pups, at P3 to P9. PBS injection does not per se induce the expression of cytokines and chemokine genes, since the equivalent levels of transcripts are observed under PBS and naïve conditions, in contrast to what is observed upon IL1B treatment. O4+ cells from naïve mice: n = 6 at P3, n = 6 at P5, n = 6 at P9; O4+ cells from PBS-injected mice: n = 2 at P5; O4+ cells from IL1B-injected mice: n = 2 at P5. Mbp serves as a positive control of the myelination process that is expected to occur in P9 in control conditions.

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