未经治疗的多发性硬化症患者脑脊液细胞的整合单细胞转录组学研究。
Integrated single-cell transcriptomics of cerebrospinal fluid cells in treatment-naïve multiple sclerosis.
机构信息
Department of Neurology with Institute of Translational Neurology, Medical Faculty, University Hospital Münster, Münster, Germany.
Department of Research, Biogen, Cambridge, MA, USA.
出版信息
J Neuroinflammation. 2022 Dec 19;19(1):306. doi: 10.1186/s12974-022-02667-9.
Multiple sclerosis (MS) is a chronic and often disabling autoimmune disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) surrounds and protects the CNS. Analysis of CSF can aid the diagnosis of CNS diseases, help to identify the prognosis, and underlying mechanisms of diseases. Several recent studies have leveraged single-cell RNA-sequencing (scRNA-seq) to identify MS-associated changes in CSF cells that are considerably more altered than blood cells in MS. However, not all alterations were replicated across all studies. We therefore integrated multiple available scRNA-seq datasets of CSF cells from MS patients with early relapsing-remitting (RRMS) disease. We provide a searchable and interactive resource of this integrated analysis ( https://CSFinMS.bxgenomics.com ) facilitating diverse visualization and analysis methods without requiring computational skills. In the present joint analysis, we replicated the known expansion of B lineage and the recently described expansion of natural killer (NK) cells and some cytotoxic T cells and decrease of monocytes in the CSF in MS. The previous observation of the abundance of Th1-like Th17 effector memory cells in the CSF was not replicated. Expanded CSF B lineage cells resembled class-switched plasmablasts/-cells (e.g., SDC1/CD138, MZB1) as expected. Our integrative analysis thus validates increased cell type diversity and B cell maturation in the CSF in MS and improves accessibility of available data.
多发性硬化症(MS)是一种慢性且常导致残疾的中枢神经系统(CNS)自身免疫性疾病。脑脊液(CSF)包围并保护中枢神经系统。CSF 的分析有助于中枢神经系统疾病的诊断,有助于确定预后和疾病的潜在机制。最近的几项研究利用单细胞 RNA 测序(scRNA-seq)来鉴定与 MS 相关的 CSF 细胞变化,这些变化在 MS 中比血细胞变化更为显著。然而,并非所有变化都在所有研究中得到复制。因此,我们整合了来自早期复发缓解型(RRMS)MS 患者的多个可用的 CSF 细胞 scRNA-seq 数据集。我们提供了一个可搜索和交互式的综合分析资源(https://CSFinMS.bxgenomics.com),无需计算技能即可方便地使用多种可视化和分析方法。在本联合分析中,我们复制了已知的 B 细胞系扩增以及最近描述的自然杀伤(NK)细胞和一些细胞毒性 T 细胞扩增和单核细胞减少在 MS 中的情况。以前在 CSF 中观察到的 Th1 样 Th17 效应记忆细胞的丰度并未得到复制。预期 CSF 中扩增的 B 细胞系细胞类似于类别转换的浆母细胞/-细胞(例如,SDC1/CD138、MZB1)。因此,我们的综合分析验证了 MS 中 CSF 中细胞类型多样性和 B 细胞成熟度的增加,并提高了现有数据的可访问性。