Cross-regional homeostatic and reactive glial signatures in multiple sclerosis

• DOI: 10.1007/s00401-022-02497-2
• Publication Date: 2022-09-16T11:03:52Z
• Authors: Tim Trobisch; Amel Zulji; Nikolas A. Stevens; Sophia Schwarz; Sven Wischnewski; Mikail Öztürk; Javier Perales-Patón; Maximilian Haeussler; Julio Saez-Rodriguez; Dmitry Velmeshev; Lucas Schirmer
• Keywords: Homeostasis

Abstract Multiple sclerosis (MS) is a multifocal and progressive inflammatory disease of the central nervous system (CNS). However, compartmentalized pathology affecting various anatomical regions including gray white matter lack appropriate models impede understanding disease. Utilizing single-nucleus RNA-sequencing multiplex spatial RNA mapping, we generated an integrated transcriptomic map comprising leukocortical, cerebellar spinal cord areas in normal MS tissues that captures regional subtype diversity cell types with emphasis on astrocytes oligodendrocytes. While found strong cross-regional among glial subtypes control tissue, signatures become more obscure MS. This suggests patterns changes are shared across converge specific pathways, especially those regulating cellular stress immune activation. In addition, evidence oligodendrocytes appearing all three CNS adopt pro-remyelinating gene summary, our data suggest overlap MS, different reactive capable either exacerbating or ameliorating pathology.