Pro-Inflammatory Molecules Implicated in Multiple Sclerosis Divert the Development of Human Oligodendrocyte Lineage Cells

作者：Gabriela J. Blaszczyk, Abdulshakour Mohammadnia, Valerio E. C. Piscopo, Julien Sirois, Qiao‐Ling Cui, Moein Yaqubi, Thomas M. Durcan, Raphaël Schneider, Jack P. Antel · 发表于：Neurology Neuroimmunology & Neuroinflammation · 年份：2025 · DOI：10.1212/nxi.0000000000200407 · 被引用次数：6 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Neuroinflammation and Neurodegeneration Mechanisms、Glioma Diagnosis and Treatment

BACKGROUND AND OBJECTIVES: ) on the differentiation of human OPCs. METHODS: and evaluated effects regarding cell viability, expression of OL lineage markers, and coexpression of astrocyte markers. To relate our findings to the molecular properties of OPCs as found in the MS brain, we reanalyzed publicly available single-nuclear RNA sequencing (RNAseq) datasets. RESULTS: decreased the proportion of cells differentiating into the OL lineage, consistent with previous reports. Uniquely, we now observe that the TNF⍺ effect is linked to aberrant OPC differentiation in that a subset of O4+, reporter-positive cells coexpressing the astrocytic marker aquaporin-4. At the transcriptomic level, the cells acquire an astrocyte-like signature alongside a conserved reactive phenotype while downregulating OL lineage genes. Analysis of single-nuclear RNAseq datasets from the human MS brain revealed a subset of OPCs expressing an astrocytic signature. DISCUSSION: In the context of MS, these results imply that OPCs are present but inhibited from differentiating along the OL lineage, with a subset acquiring a reactive and stem cell-like phenotype, reducing their capacity to contribute toward repair. These findings help define a potential basis for the impaired myelin repair in MS and provide a prospective route for regenerative treatment.