Astrocyte Heterogeneity in Multiple Sclerosis: Current Understanding and Technical Challenges

Abstract

The emergence of single cell technologies provides the opportunity to characterize complex immune/central nervous system cell assemblies in multiple sclerosis (MS) and to study their cell population structures, network activation and dynamics at unprecedented depths. In this review, we summarize the current knowledge of astrocyte subpopulations in MS tissue and discuss the challenges associated with resolving astrocyte heterogeneity with single-nucleus RNA-sequencing (snRNA-seq). We further discuss multiplexed imaging techniques as tools for defining population clusters within a spatial context. Finally, we will provide an outlook on how these technologies may aid in answering unresolved questions in MS, such as the glial phenotypes that drive MS progression and/or neuropathological differences between different clinical MS subtypes.

S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis

“…Astrocytes are known to play active roles in neurodegenerative disorders [39,44] and in MS in particular [45]; thus, a protective effect involving this cell type cannot be regarded as unexpected. Additional experiments will be needed to explore in detail possible effects of AA on this cell type, not only having in mind its effects on S100B synthesis/secretion, but also considering its heterogeneity [46].…”

Navigating the cellular landscape in tissue: Recent advances in defining the pathogenesis of human disease

“…The limited availability of high-quality samples of early and active disease has led to difficulties in characterizing this stage of disease [65] . Multiplex imaging technologies have enabled the study of immune and CNS cell interactions while simultaneously generating high parameter data from rare archival samples [66] .…”

Myelin repair is fostered by the corticosteroid medrysone specifically acting on astroglial subpopulations

“… 2 , 3 This also holds true for nearby neurogenic stem cell niches, such as the subventricular zone (SVZ), with gliosis, and its upgrading inflammation leading to NSCs depletion. 3 , 4 , 5 As these NSCs contribute to neuronal, oligodendroglial and astroglial cell populations, thereby supporting axon integrity, neuronal communication and myelination this must be considered as a substantial impact. 6 , 7 , 8 Oligodendroglial cells are preferentially generated within the dorsal region (d-SVZ) 7 , 8 , 9 , 10 whereas astrocytes mainly develop from the lateral SVZ.…”

“…1 Moreover, astrocyte activation and gliosis are observed additionally modulating endogenous repair processes. 2,3 This also holds true for nearby neurogenic stem cell niches, such as the subventricular zone (SVZ), with gliosis, and its upgrading inflammation leading to NSCs depletion. 3À5 As these NSCs contribute to neuronal, oligodendroglial and astroglial cell populations, thereby supporting axon integrity, neuronal communication and myelination this must be considered as a substantial impact.…”