Spatial transcriptomics reveal heterogeneous cell‒cell interactions among brain regions in cuprizone model consistent with multiple sclerosis lesions
Year: 2026
Type: article
Abstract: The cuprizone (CPZ) model is widely used for modeling demyelination in multiple sclerosis (MS) and for testing potential remyelination therapies. We integrated single-cell and spatial transcriptomics (ST) to fine map the spatial cellular and molecular responses during de and remyelination. ST revealed global demyelination and neuroinflammation in the brain beyond the corpus callosum, with region-specific differences. We identified oligodendroglia and microglia as two major cell types with significant transcriptomic changes in the model. Ligand receptor pairing analyses predicted growth factor and phagocytic pathway enrichment during demyelination, which is consistent with changes in MS lesions. During remyelination, while mature oligodendrocytes nearly reversed their phenotype back to the control state, microglia remained associated with the demyelination phenotype. Finally, astrocytes in the CPZ model had the greatest preservation of disease-associated modules to MS lesions, while the MOL, OPC, and microglia showed moderate to low preservation, which overall suggested that the CPZ model had moderate translatability to chronically active MS lesions.
Source: Frontiers in Bioinformatics
Authors: Hui-Hsin Tsai, Sarbottam Piya, Jing Wang, Jing Zhu, Wenxing Hu, Andrew R. Gehrke, Shaolong Cao, Amanda J. Guise, Su Jing Chan, Mark Sheehan, Jenhwa Chu, Zhengyu Ouyang, Matthew Ryals, Michelle Lee, Wanli Wang, Edward Zhao, Patrick Cullen, Ravi Challa, Eric Marshall, Wanyong Zeng, Yea Jin Kaeser-Woo, Chris Ehrenfels, Luke Jandreski, Helen McLaughlin, Thomas M. Carlile, Jake Gagnon, Taylor L. Reynolds, Mingyao Li, Kejie Li, Baohong Zhang
Institutions: Biogen (United States), University of Pennsylvania
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,077
OpenAlex ID: W7196962003