RiboTag-based RNA-Seq uncovers oligodendroglial lineage-specific inflammation in autoimmune encephalomyelitis

Yuhang Wang; Sudeep Ghimire; Ashutosh Mangalam; Zizhen Kang

doi:10.1101/2024.12.24.630168

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RiboTag-based RNA-Seq uncovers oligodendroglial lineage-specific inflammation in autoimmune encephalomyelitis

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RiboTag-based RNA-Seq uncovers oligodendroglial lineage-specific inflammation in autoimmune encephalomyelitis

Yuhang Wang, Sudeep Ghimire, Ashutosh Mangalam and Zizhen Kang

bioRxiv

Cold Spring Harbor Laboratory, 1.2

12/26/2024

DOI: 10.1101/2024.12.24.630168

PMCID: PMC11703255

PMID: 39764033

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https://doi.org/10.1101/2024.12.24.630168View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Oligodendroglial lineage cells (OLCs) are critical for neuronal support functions, including myelination and remyelination. Emerging evidence reveals their active roles in neuroinflammation, particularly in conditions like Multiple Sclerosis (MS). This study explores the inflammatory translatome of OLCs during the early onset of experimental autoimmune encephalomyelitis (EAE), an established MS model. Using RiboTag-based RNA sequencing in genetically modified Olig2-Cre RiboTag mice, we identified 1,556 upregulated and 683 downregulated genes in EAE OLCs. Enrichment analysis indicated heightened immune-related pathways, such as cytokine signaling, interferon responses, and antigen presentation, while downregulated genes were linked to neuronal development and myelination. Notably, OLCs expressed cytokines/chemokines, and their receptor, highlighting their active involvement in neuroinflammatory signaling. Functional studies demonstrated that interferon-gamma (IFN-γ) signaling in OLCs exacerbates EAE pathology by enhancing antigen presentation and chemokine production, whereas interferon-beta (IFN-β) signaling showed minimal impact. These findings provide novel insights into the inflammatory role of OLCs in EAE and suggest therapeutic potential in targeting OLC-mediated neuroinflammation for MS and related disorders.

Immunology

Details

Title: Subtitle: RiboTag-based RNA-Seq uncovers oligodendroglial lineage-specific inflammation in autoimmune encephalomyelitis
Creators: Yuhang Wang - University of Iowa
Sudeep Ghimire - University of Iowa
Ashutosh Mangalam - University of Iowa
Zizhen Kang - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Edition: 1.2
DOI: 10.1101/2024.12.24.630168
PMID: 39764033
PMCID: PMC11703255
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Number of pages: 24
Language: English
Date posted: 12/26/2024
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984772247102771

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