Figure 6.

Microglia might impede remyelination via Stat1 pathway in aged CNS. (A) Heatmap of enrichment scores derived from GSEA showing the C3 subset of microglia suppressed OPC differentiation. Numbers in legend represented scaled enrichment scores. (B) Violin plot depicting expression of ligands identified to promote remyelination (first line) or impede OPC differentiation (second line) in aged microglia cluster. The third line showed that aged microglia did not highly express Vegfb, Igf1, Tnf or Il1b. (C) Network plot showing interactions between cytokines in panel (B) and their possible transcription factors inferred from TRRUST, yellow for cytokines and blue for transcription factors. (D) Heatmap derived from pySCENIC package showing the activity scores of different transcription factors in microglia C3 compared with the C0 subset. Values were normalized per gene. (E) Representative confocal microscopic images in young and old cortex staining for IBA1 and pSTAT1. DAPI labels cell nuclei. Scale bar: 50μm or 25 μm. Bar plots depicting the percent of pSTAT1+ microglia (**** P-value < 0.0001 by student’s t test. n = 5 samples per condition). (F) Schematic diagram depicting that Stat1 might regulate the production of different cytokines (upregulate Apoe and downregulate Spp1, Lgals3, Igf1 and Lpl) in microglia. Those cytokines acted on OPCs and OLGs alternatively, evoking OLG remyelination and impeding the differentiation process of OPCs.

Abbreviations: CNS, central nervous system; GSEA, Gene Set Enrichment Analysis; ES, enrichment score; pSTAT1, phosphorylated STAT1; OPCs, oligodendrocyte precursor cells; OLGs, oligodendrocytes; MG, microglia.