학술논문

Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology
Document Type
Source
Cell. 187(8):1990-2009
Subject
spatial sequencing
in situ sequencing
single-cell
experimental autoimmune
encephalomyelitis
EAE
multiple sclerosis
MS
neuropathology
neuroinflammation disease-associated glia
Serpina3n
SERPINA3
Language
English
ISSN
2019-0107
Abstract
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.