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科学家发现ALS疾病潜在预测指标
作者:小柯机器人 发布时间:2021/4/17 20:33:16

瑞典KTH皇家技术学院Sebastian A. Lewandowski研究组取得一项新突破。他们发现肌萎缩性侧索硬化症(ALS)疾病发作之前血管周成纤维细胞活性改变。该研究于2021年4月15日发表于国际一流学术期刊《自然-医学》。

他们使用表达加权细胞类型富集方法来推断散发性ALS患者和该病小鼠模型的脊髓样品中的细胞活性。他们报告散发性ALS的患者表现出与两种小鼠模型一致的细胞活性模式,在该模型中,血管细胞基因的富集先于小胶质细胞反应。值得注意的是,在症状发作前阶段,散发性ALS患者的血管周成纤维细胞显示出最强的基因富集,其标志物蛋白SPP1和COL6A1在扩大的血管周空间中聚集。

此外,在来自四个独立队列的574例ALS患者的血浆中,疾病诊断时SPP1水平的升高反复预测的生存期更短,其效果要比脑脊髓液中延髓发作或神经丝水平的既定危险因素高。他们建议,最近发现的血管周成纤维细胞的活性可以预测ALS患者的生存,并提供一个新的概念框架来重新评估ALS病因的定义。

研究人员表示,除了神经元细胞中定义明确的因素外,只有少数报道认为散发性ALS进展的变异性可能取决于神经胶质细胞和血管的不确定性贡献。

附:英文原文

Title: Altered perivascular fibroblast activity precedes ALS disease onset

Author: Anna Mnberg, Nathan Skene, Folkert Sanders, Marta Trusohamn, Julia Remnestl, Anna Szczepiska, Inci Sevval Aksoylu, Peter Lnnerberg, Lwaki Ebarasi, Stefan Wouters, Manuela Lehmann, Jennie Olofsson, Inti von Gohren Antequera, Aylin Domaniku, Maxim De Schaepdryver, Joke De Vocht, Koen Poesen, Mathias Uhln, Jasper Anink, Caroline Mijnsbergen, Hermieneke Vergunst-Bosch, Annemarie Hbers, Ulf Klppe, Elena Rodriguez-Vieitez, Jonathan D. Gilthorpe, Eva Hedlund, Robert A. Harris, Eleonora Aronica, Philip Van Damme, Albert Ludolph, Jan Veldink, Caroline Ingre, Peter Nilsson, Sebastian A. Lewandowski

Issue&Volume: 2021-04-15

Abstract: Apart from well-defined factors in neuronal cells1, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia2,3 and blood vessels4. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response. Notably, during the presymptomatic stage, perivascular fibroblast cells showed the strongest gene enrichments, and their marker proteins SPP1 and COL6A1 accumulated in enlarged perivascular spaces in patients with sporadic ALS. Moreover, in plasma of 574 patients with ALS from four independent cohorts, increased levels of SPP1 at disease diagnosis repeatedly predicted shorter survival with stronger effect than the established risk factors of bulbar onset or neurofilament levels in cerebrospinal fluid. We propose that the activity of the recently discovered perivascular fibroblast can predict survival of patients with ALS and provide a new conceptual framework to re-evaluate definitions of ALS etiology. Increased perivascular fibroblast activity and vascular remodeling occurs early in ALS pathogenesis and can predict patient survival time.

DOI: 10.1038/s41591-021-01295-9

Source: https://www.nature.com/articles/s41591-021-01295-9

 

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex