Spatial multi-omics reveals disease-associated oligodendrocytes and metabolic dysregulation in male Parkinson’s disease mouse models
6 affiliations
- 1Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120 China
- 2School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436 China
- 3State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, 511436 China
- 4Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou, 511436 China
- 5The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang China
- 6Department of Neurology, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021 China
Abstract
Parkinson’s disease involves progressive α-synuclein pathology, but how this reshapes the brain’s spatial immunometabolic landscape, and how oligodendrocytes participate, remain incompletely defined. Here we combine single-nucleus RNA sequencing, spatial transcriptomics and spatial metabolomics in male A53T α-synuclein transgenic mice across disease stages, together with male mice carrying adeno-associated virus-mediated α-synuclein overexpression, human midbrain and cerebrospinal fluid samples. We describe a disease-associated oligodendrocyte lineage marked by elevated Il33 and Kirrel3 that expands with pathology in both mouse models. Interleukin 33 is upregulated in oligodendrocytes and its receptor ST2 in microglia, and bidirectional manipulation of oligodendrocyte Il33 alters microglial ST2 activation, insoluble α-synuclein burden and motor performance. In the substantia nigra and ventral tegmental area, transcriptomic and metabolomic changes converge on lipid- and glutamate-related pathways. Both proteins are also elevated in human Parkinson’s disease midbrain and cerebrospinal fluid. These data implicate oligodendrocyte interleukin 33–ST2 signalling and provide a spatially resolved resource.
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BibTeX
@article{zhu2026spatial,
title = {{Spatial multi-omics reveals disease-associated oligodendrocytes and metabolic dysregulation in male Parkinson’s disease mouse models}},
author = {Ziting Zhu and Zongtang Xu and Minshan Chen and Liuyan Ding and Du Feng and Fengchu Liang and Hui Shu and Zhongqiang Su and Xingting Huang and Xiaoqin Zhu and Xiaolei Liang and Shuxuan Huang and Pingyi Xu and Wenlong Zhang},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-78051-5},
url = {https://doi.org/10.1038/s41467-026-78051-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Spatial multi-omics reveals disease-associated oligodendrocytes and metabolic dysregulation in male Parkinson’s disease mouse models
AU - Ziting Zhu
AU - Zongtang Xu
AU - Minshan Chen
AU - Liuyan Ding
AU - Du Feng
AU - Fengchu Liang
AU - Hui Shu
AU - Zhongqiang Su
AU - Xingting Huang
AU - Xiaoqin Zhu
AU - Xiaolei Liang
AU - Shuxuan Huang
AU - Pingyi Xu
AU - Wenlong Zhang
PY - 2026
DA - 2026/09/25
JO - Nature Communications
DO - 10.1038/s41467-026-78051-5
UR - https://doi.org/10.1038/s41467-026-78051-5
AB - Parkinson’s disease involves progressive α-synuclein pathology, but how this reshapes the brain’s spatial immunometabolic landscape, and how oligodendrocytes participate, remain incompletely defined. Here we combine single-nucleus RNA sequencing, spatial transcriptomics and spatial metabolomics in male A53T α-synuclein transgenic mice across disease stages, together with male mice carrying adeno-associated virus-mediated α-synuclein overexpression, human midbrain and cerebrospinal fluid samples. We describe a disease-associated oligodendrocyte lineage marked by elevated Il33 and Kirrel3 that expands with pathology in both mouse models. Interleukin 33 is upregulated in oligodendrocytes and its receptor ST2 in microglia, and bidirectional manipulation of oligodendrocyte Il33 alters microglial ST2 activation, insoluble α-synuclein burden and motor performance. In the substantia nigra and ventral tegmental area, transcriptomic and metabolomic changes converge on lipid- and glutamate-related pathways. Both proteins are also elevated in human Parkinson’s disease midbrain and cerebrospinal fluid. These data implicate oligodendrocyte interleukin 33–ST2 signalling and provide a spatially resolved resource.
SN - 2041-1723
ER -