Acta Neuropathologica, 2022 · DOI: https://doi.org/10.1007/s00401-022-02497-2 · Published: September 16, 2022
Multiple sclerosis (MS) is a multifocal and progressive inflammatory disease of the central nervous system (CNS). However, the compartmentalized pathology of the disease affecting various anatomical regions including gray and white matter and lack of appropriate disease models impede understanding of the disease. Utilizing single-nucleus RNA-sequencing and multiplex spatial RNA mapping, we generated an integrated transcriptomic map comprising leukocortical, cerebellar and spinal cord areas in normal and MS tissues that captures regional subtype diversity of various cell types with an emphasis on astrocytes and oligodendrocytes. In summary, our data suggest that cross-regional transcriptomic glial signatures overlap in MS, with different reactive glial cell types capable of either exacerbating or ameliorating pathology.
Identifying spatial subtypes would catalyze the development of region- and cell type-specific biomarkers and help design targeted treatments to tackle specific cell types involved in progressive MS.
The unbiased in silico approach was able to identify a white matter-specific oligodendrocyte subtype that was associated with previously discovered pro-myelinating therapeutic target gene expression.
Independent of a pharmacological treatment approach, oligodendrocytes transform into a reactive state, in which pro-myelinating pathways are turned on in the context of chronic inflammatory demyelination.