近日，瑞典斯德哥尔摩大学教授Gonalo Castelo-Branco及其研究组，报道了发展中的神经炎性病变和多发性硬化症病理的细胞结构。该项研究成果发表在2024年3月20日出版的《细胞》上。
研究人员通过通过模拟小鼠实验性自身免疫性脑脊髓炎(EAE)的时间和区域疾病进展率，来研究多发性硬化症的细胞动力学。通过执行单细胞空间表达谱主题化原位测序(ISS)，该课题组人员注释了疾病邻近区域，并发现了活动病变的离心进化。课题组研究人员证明了疾病相关(DA)-胶质细胞独立于病变而产生，并在疾病本身中动态诱导和消退。
人类归档的多发性硬化症脊髓的单细胞空间图谱，证实了稳态和疾病相关胶质细胞的差异分布，使活动性和非活动性病变反卷积到亚区室，并确定了新的病变区域。通过在单细胞分辨率上建立小鼠和人类多发性硬化症神经病理学的空间资源，他们的研究揭示了多发性硬化症背后复杂的细胞动力学。
研究人员表示，多发性硬化症(MS)是一种以多灶性病变和郁积性病理为特征的神经系统疾病。虽然单细胞分析提供了细胞病理学的见解，但MS背后的细胞进化过程仍然知之甚少。
Title: Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology
Author: Petra Kukanja, Christoffer M. Langseth, Leslie A. Rubio Rodríguez-Kirby, Eneritz Agirre, Chao Zheng, Amitha Raman, Chika Yokota, Christophe Avenel, Katarina Tiklová, André O. Guerreiro-Cacais, Tomas Olsson, Markus M. Hilscher, Mats Nilsson, Gonalo Castelo-Branco
Issue&Volume: 2024-03-20
Abstract: Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single-cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the cellular dynamics of MS by modeling temporal and regional rates of disease progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing single-cell spatial expression profiling using in situ sequencing (ISS), we annotated disease neighborhoods and found centrifugal evolution of active lesions. We demonstrated that disease-associated (DA)-glia arise independently of lesions and are dynamically induced and resolved over the disease course. Single-cell spatial mapping of human archival MS spinal cords confirmed the differential distribution of homeostatic and DA-glia, enabled deconvolution of active and inactive lesions into sub-compartments, and identified new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single-cell resolution, our study unveils the intricate cellular dynamics underlying MS.
DOI: 10.1016/j.cell.2024.02.030
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00233-2