Table_1_High-Resolution Transcriptomic and Proteomic Profiling of Heterogeneity of Brain-Derived Microglia in Multiple Sclerosis.DOCX

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.

小胶质细胞（Microglia）对中枢神经系统（central nervous system, CNS）的稳态维持至关重要，且是率先响应组织损伤与扰动的细胞类群。小胶质细胞是一类具有异质性的细胞；在病理状态下，小胶质细胞会呈现多种功能改变的表型。然而，这些不同的小胶质细胞亚型如何参与中枢神经系统疾病的发生发展，目前仍未完全阐明。多发性硬化（Multiple sclerosis, MS）是一种发生于中枢神经系统的慢性脱髓鞘疾病，以炎症与轴突变性为特征，最终可导致神经功能衰退。小胶质细胞参与多发性硬化的途径之一是促进髓鞘再生：它们可通过吞噬髓鞘碎片，高效推动髓鞘再生过程。此外，小胶质细胞可招募少突胶质前体细胞（oligodendrocyte precursor cells, OPCs）至脱髓鞘区域，并刺激髓鞘再生。用于表征单个细胞的高分辨率技术的发展，极大推动了我们对正常与病理状态下小胶质细胞异质性及其功能的认知。基因表达谱分析技术已从整体组织RNA测序，逐步发展至单细胞或单细胞核测序技术。当前单小胶质细胞蛋白质组谱的构建也日益增多，为研究提供了另一维度的高分辨率数据。本文将综述近年来利用这些技术开展的多发性硬化相关研究，以及各技术各自的优缺点。此外，本文还将探讨可在保留空间信息与组织背景的前提下实现（单）细胞谱分析的最新技术进展。