High-Resolution Transcriptomic and Proteomic Profiling of Heterogeneity of Brain-Derived Microglia in Multiple Sclerosis

Abstract

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Microglia are important for central nervous system (CNS) homeostasis and first to respond to tissue damage and perturbations. Microglia are heterogeneous cells; in case of pathology, microglia adopt a range of phenotypes with altered functions. However, how these different microglia subtypes are implicated in CNS disease is largely unresolved. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS, characterized by inflammation and axonal degeneration, ultimately leading to neurological decline. One way microglia are implicated in MS is through stimulation of remyelination. They facilitate efficient remyelination by phagocytosis of myelin debris. In addition, microglia recruit oligodendrocyte precursor cells (OPCs) to demyelinated areas and stimulate remyelination. The development of high-resolution technologies to profile individual cells has greatly contributed to our understanding of microglia heterogeneity and function under normal and pathological conditions. Gene expression profiling technologies have evolved from whole tissue RNA sequencing toward single-cell or nucleus sequencing. Single microglia proteomic profiles are also increasingly generated, offering another layer of high-resolution data. Here, we will review recent studies that have employed these technologies in the context of MS and their respective advantages and disadvantages. Moreover, recent developments that allow for (single) cell profiling while retaining spatial information and tissue context will be discussed.

Keywords

• multiple sclerosis
• microglia
• heterogeneity
• spatial
• sequencing