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.
Highlights
Due to the resounding success of current MS medications in treating relapsing-remitting MS (RRMS), research interest is increasingly focused on disease progression and neurorepair where current treatments are ineffective
Highly multiplexed protein imaging has a parametric depth of only dozens to perhaps hundreds of markers, but allows for precise outlining of cells with complex, irregular morphologies such as astrocytes, which will improve the spatial analysis of individual cells
We observed that several key markers of astrocytes and microglia activation that were readily detectable with multiplexed imaging, were absent in singlecell transcriptomic datasets from MS lesions
Summary
Due to the resounding success of current MS medications in treating relapsing-remitting MS (RRMS), research interest is increasingly focused on disease progression and neurorepair where current treatments are ineffective. The transcriptomic clusters correspond to distinct morphological features and spatial distribution and have implications for different physiological functions These studies have focused on cortical astrocytes and less is known about astrocyte diversity in white matter (Köhler et al, 2021). Green fluorescent protein (GFP)-labeled astrocytes were isolated and screened for 81 cell surface antigens with fluorescence-activated cell sorting (FACS) (John Lin et al, 2017) This identified five distinct astrocyte subpopulations present across cortex, brainstem, and olfactory bulb, which were subsequently demonstrated to emerge at different developmental stages and to have distinct geneenrichment and functional properties.
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