A 4D transcriptomic map for the evolution of multiple sclerosis-like lesions in the marmoset brain

Conventional single timepoint studies on postmortem MS tissue, conducted decades after lesion initiation, do not capture evolving cellular dynamics within the lesions. While several preclinical animal models of MS have provided insights, the extensively studied mouse EAE model often lacks key features of MS, including brain lesions and humoral immune responses. To address this gap, I utilized the marmoset EAE, a faithful MS animal model closely mirroring key aspects of lesion evolution in MS. I performed a cross-modality analysis to generate a comprehensive neuroglial map of the marmoset brain during inflammation, identifying distinct microenvironments during myelin loss and recovery. Additionally, I introduced a novel radiological biomarker for detecting impending lesion formation and expansion. This forms a crucial foundation for developing clinically relevant methods to monitor and predict lesion outcomes for treatment evaluation using the marmoset as a platform.

Citation: Lin JP*, Brake A, Donadieu M, Lee A, Smith G, Hu K, Nair G, Kawaguchi R, Sati P, Geschwind DH, Jacobson S, Schafer DP, Reich DS*. Science 2025 Feb
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