Diversity and Function of Glial Cell Types in Multiple Sclerosis. Issue 3 (March 2021)

• Record Type: Journal Article
• Authors: Schirmer, Lucas; Schafer, Dorothy P.; Bartels, Theresa; Rowitch, David H.; Calabresi, Peter A.
• Is Part Of: Trends in immunology. Volume 42:Issue 3(2021)
• Page Start: 228
• Page End: 247
• Publication Date: 2021-03
• Subjects: oligodendrocytes -- astrocytes -- microglia -- transcriptomics -- multiple sclerosis -- neuroinflammation; Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2021.01.005
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Glial subtype diversity is an emerging topic in neurobiology and immune-mediated neurological diseases such as multiple sclerosis (MS). We discuss recent conceptual and technological advances that allow a better understanding of the transcriptomic and functional heterogeneity of oligodendrocytes (OLs), astrocytes, and microglial cells under inflammatory–demyelinating conditions. Recent single cell transcriptomic studies suggest the occurrence of novel homeostatic and reactive glial subtypes and provide insight into the molecular events during disease progression. Multiplexed RNA in situ hybridization has enabled 'mapping back' dysregulated gene expression to glial subtypes within the MS lesion microenvironment. These findings suggest novel homeostatic and reactive glial-cell-type functions both in immune-related processes and neuroprotection relevant to understanding the pathology of MS. Highlights: Single-cell transcriptomic technologies have revolutionized our understanding of homeostatic and reactive glial cell types during disease progression in experimental models and in human multiple sclerosis (MS) tissue samples, which can reflect different stages of tissue damage. Homeostatic and reactive glial cell types show intra- and inter-regional heterogeneity in different central nervous system (CNS) areas and within inflammatory–demyelinating lesions. Reactive glial subtypes are highly polarized based on morphological, transcriptomic, and functional criteria, having seemingly opposing roles in either promoting or suppressing inflammation and further tissue damage. Glial subtype-specific transcriptomic profiling has helped identify novel homeostatic and reactive subtype markers that will be useful for the development of novel biomarkers and therapeutic targets for future studies in MS.