多发性硬化症小鼠模型疾病进展过程中成熟少突胶质细胞的不同转录组和表观基因组反应，这一成果由瑞典卡罗林斯卡学院Gonçalo Castelo-Branco小组经过不懈努力而取得。2025年11月17日出版的《自然—神经科学》发表了这项成果。

该课题组研究人员对来自实验性自身免疫性脑脊髓炎（EAE） MS小鼠模型的不同疾病阶段的少突胶质细胞（OLG）进行了转座酶可及染色质和RNA测序的单细胞多组测定。研究人员发现免疫OLG状态出现在疾病早期，并持续到晚期，这可能与先前神经炎症的表观遗传记忆一致。转录因子活性提示OLG在疾病早期有免疫抑制。不同的MOLs对EAE表现出不同的反应，其中MOL2表现出比MOL5/MOL6更强的转录免疫反应，并且在疾病进化过程中表现出不同的表观遗传水平反应。它们的单细胞多组抗性突出了OLG对EAE的动态和亚型特异性反应，这可能是MS调节的结果。

据了解，多发性硬化症（MS）是一种以成熟少突胶质细胞（MOLs）及其髓磷脂为靶点的慢性自身免疫性疾病。MOLs是异质的，在多发性硬化症中可以转变为免疫样状态。然而，这一过程的动态仍不清楚。

附：英文原文

Title: Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis

Author: Zheng, Chao, Herv, Bastien, Meijer, Mandy, Rubio Rodrguez-Kirby, Leslie Ann, Guerreiro Cacais, Andr Ortlieb, Kukanja, Petra, Kabbe, Mukund, Jimenez-Beristain, Tony, Olsson, Tomas, Agirre, Eneritz, Castelo-Branco, Gonalo

Issue&Volume: 2025-11-17

Abstract: Multiple sclerosis (MS) is a chronic autoimmune disease that targets mature oligodendrocytes (MOLs) and their myelin. MOLs are heterogeneous and can transition to immune-like states in MS. However, the dynamics of this process remain unclear. Here, we used single-cell multiome assay for transposase-accessible chromatin and RNA sequencing targeting oligodendroglia (OLG) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model at multiple disease stages. We found that immune OLG states appear at early disease stages and persist to late stages, which can be consistent with epigenetic memory of previous neuroinflammation. Transcription factor activity suggested immunosuppression in OLG at early disease stages. Different MOLs exhibit differential responsiveness to EAE, with MOL2 exhibiting a stronger transcriptional immune response than MOL5/MOL6, and showed divergent responses at the epigenetic level during disease evolution. Our single-cell multiomic resource highlights dynamic and subtype-specific responses of OLG to EAE, which might be amenable to modulation in MS.

DOI: 10.1038/s41593-025-02100-3

Source: https://www.nature.com/articles/s41593-025-02100-3