snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

IF 14.7 1区 医学 Q1 NEUROSCIENCES Neuron Pub Date : 2024-12-19 DOI:10.1016/j.neuron.2024.11.016
Will Macnair, Daniela Calini, Eneritz Agirre, Julien Bryois, Sarah Jäkel, Rebecca Sherrard Smith, Petra Kukanja, Nadine Stokar-Regenscheit, Virginie Ott, Lynette C Foo, Ludovic Collin, Sven Schippling, Eduard Urich, Erik Nutma, Manuel Marzin, Federico Ansaloni, Sandra Amor, Roberta Magliozzi, Elyas Heidari, Mark D Robinson, Charles Ffrench-Constant, Gonçalo Castelo-Branco, Anna Williams, Dheeraj Malhotra
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引用次数: 0

Abstract

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences. MS lesion subtypes had different cellular compositions but surprisingly similar cell-type gene expression patterns both within and across patients, suggesting global changes. Most gene expression variability was instead explained by patient effects, allowing us to stratify patients and describe the different pathological processes occurring between patient subgroups. Future mapping of these brain molecular profiles with blood and/or CSF profiles from living MS patients will allow precision medicine approaches anchored in patient-specific pathological processes.

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来源期刊
Neuron
Neuron 医学-神经科学
CiteScore
24.50
自引率
3.10%
发文量
382
审稿时长
1 months
期刊介绍: Established as a highly influential journal in neuroscience, Neuron is widely relied upon in the field. The editors adopt interdisciplinary strategies, integrating biophysical, cellular, developmental, and molecular approaches alongside a systems approach to sensory, motor, and higher-order cognitive functions. Serving as a premier intellectual forum, Neuron holds a prominent position in the entire neuroscience community.
期刊最新文献
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