Integrative single cell analysis of progressive multiple sclerosis induced neural stem cells reveals epigenetically dysregulated type-I-interferon signaling [WGBS]

We next identified a unique subcluster of cells within the PMS iNSCs that have a pro-inflammatory and senescent phenotype, associated with interferon gene activation using sc-RNA seq. Within this specific subcluster there is higher expression of genes associated with inflammatory protein secretion, as well as the senescence associated secretory phenotype (SASP). A similar clustering pattern was observed in the ATAC-seq data, a large main cluster and a small inflammatory cluster primarily comprising of PMS iNSCs.

Differentially accessible regions within the PMS cluster revealed promoter sites of inflammatory-associated genes to be more accessible correlating with gene expression. Our results highlight a novel cellular mechanism in PMS wherein NSCs are interferon-responsive and senescent-like which may impact other cells within the lesion leading to chronic inflammation.