Fig. 6: Centrifugal propagation of cellular senescent transcriptional signatures by spatial transcriptomics.

a Representative expression of inflammatory (SPP1, C3) and senescence-associated genes (SERPINA3, HMGB1, IGFBP5, and CDKN1A) in different MS pathological tissue (i.e., active lesion, CAL, chronic inactive lesion, remyelinated lesion, and non-lesional MS tissue). b Gradients of senescence-associated astrocyte signature (55 genes)²² was observed extending from the lesional areas toward the periplaque in Visium slides with CAL and chronic inactive lesions. c, d Spatial differential expression analysis of genes along a linear trajectory identified non-random gene gradients (SPARKX p < 0.01). Error bands of line plots indicate the confidence interval (level 0.95). Cellular senescence-related genes and SenMayo genelist exhibited non-random gradients not only within lesional areas but also in the surrounding periplaque in chronic active lesion slide V01, whereas such pattern was not observed in the active lesion slide V05. e SenMayo genelists spatial gradient for Visium slide, including a remyelinated lesion. Error bands of line plots indicate the confidence interval (level 0.95). Remyelination was assessed by both lipid staining (LFB) and myelin PLP immunostaining. The asterisk indicates the postcapillary central venule. CAL chronic active lesion, MBP myelin basic protein, LFB luxol fast blue, WM white matter, PLP myelin proteolipid protein.