Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology

• Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single -cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the cellular dynamics of MS by modeling temporal and regional rates of disease progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing single -cell spatial expression profiling using in situ sequencing (ISS), we annotated disease neighborhoods and found centrifugal evolution of active lesions. We demonstrated that disease -associated (DA)-glia arise independently of lesions and are dynamically induced and resolved over the disease course. Single -cell spatial mapping of human archival MS spinal cords confirmed the differential distribution of homeostatic and DA-glia, enabled deconvolution of active and inactive lesions into sub -compartments, and identified new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single -cell resolution, our study unveils the intricate cellular dynamics underlying MS.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

spatial sequencing

in situ sequencing

single-cell

experimental autoimmune

encephalomyelitis

EAE

multiple sclerosis

MS

neuropathology

neuroinflammation disease-associated glia

Serpina3n

SERPINA3

Publication and Content Type

ref (subject category)

art (subject category)