A 4D transcriptomic map for the evolution of multiple sclerosis-like lesions in the marmoset brain.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
27 Sep 2023
27 Sep 2023
Historique:
medline:
9
10
2023
pubmed:
9
10
2023
entrez:
9
10
2023
Statut:
epublish
Résumé
Single-time-point histopathological studies on postmortem multiple sclerosis (MS) tissue fail to capture lesion evolution dynamics, posing challenges for therapy development targeting development and repair of focal inflammatory demyelination. To close this gap, we studied experimental autoimmune encephalitis (EAE) in the common marmoset, the most faithful animal model of these processes. Using MRI-informed RNA profiling, we analyzed ~600,000 single-nucleus and ~55,000 spatial transcriptomes, comparing them against EAE inoculation status, longitudinal radiological signals, and histopathological features. We categorized 5 groups of microenvironments pertinent to neural function, immune and glial responses, tissue destruction and repair, and regulatory network at brain borders. Exploring perilesional microenvironment diversity, we uncovered central roles of EAE-associated astrocytes, oligodendrocyte precursor cells, and ependyma in lesion formation and resolution. We pinpointed imaging and molecular features capturing the pathological trajectory of WM, offering potential for assessing treatment outcomes using marmoset as a platform.
Identifiants
pubmed: 37808784
doi: 10.1101/2023.09.25.559371
pmc: PMC10557631
pii:
doi:
Types de publication
Preprint
Langues
eng
Déclaration de conflit d'intérêts
D.S.R. has received research funding from Abata and Sanofi, unrelated to the current study.
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