2024-12-20 カロリンスカ研究所
<関連情報>
- https://news.ki.se/ms-brain-atlas-could-pave-the-way-for-personalised-treatment
- https://www.cell.com/neuron/fulltext/S0896-6273(24)00873-0
snRNA-seqは多発性硬化症患者を異なる白質グリア反応に層別化する snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses
Will Macnair∙ Daniela Calini∙ Eneritz Agirre∙ … ∙ Gonçalo Castelo-Branco∙ Anna Williams∙ Dheeraj Malhotra
Neuron Published:December 20, 2024
DOI:https://doi.org/10.1016/j.neuron.2024.11.016
Graphical abstract
Highlights
•snRNA-seq atlas of multiple sclerosis brain white and gray matter versus control
•Patient-specific glial gene expression patterns stratify MS patients
•Findings support precision medicine approaches for MS
Summary
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.
