Fig. 3: poly-GA transgene induces a DOL signature which is rescued by CD treatment.

a Heatmap of previously published DOL genes¹⁴ across oligodendrocyte clusters comparing transgenic effect (n = 3 Tg Vehicle vs n = 4 WT Vehicle) and CD effect (n = 4 Tg CD vs n = 3 Tg Vehicle) as well as bulk RNAseq from the endstage GA-Nes mice (data from³⁴, 5 control vs 5 GA-Nes mice) demonstrates induction of DOL genes in the diseased state. CD treatment showcases an appreciable and significant rescue of many of these genes. Asterisks indicate significant changes (p < 0.05). b Volcano plots of the two mature oligodendrocyte clusters demonstrate some overlap with previously published DOL genes as well as other genes such as ApoD, where they get rescued by CD treatment. c SerpinA3N immunofluorescence demonstrates that increased expression of this key DOL marker in transgenic GA-Nes mice is curtailed by CD treatment, confirming the snRNAseq results. Scale bars = 50 µm. Images are representative of two independent experiments. d, e Western blot of hindbrains (n from independent biological replicates: WT vehicle = 3, WT CD = 4, Tg Vehicle = 3, Tg CD = 4) and its quantification confirms the significant induction of Serpin A3N upon transgene expression and its significant rescue upon CD treatment (ANOVA, post hoc by Tukey’s HSD). f IL33, another key DOL marker, measured by MSD V-Plex cytokine panel from hindbrain lysates shows significant modulation of this marker. Post-hoc analysis with Tukey’s HSD highlights upregulation of IL33 in the transgenic condition, which is fully rescued upon CD treatment. The treatment does not modulate IL33 levels in wild-type mice. n from independent biological replicates: WT Vehicle = 4, WT CD = 4, Tg Vehicle = 3, Tg CD = 4.