# Integrative transcriptomic analysis reveals oligodendrocyte lineage switching in multiple sclerosis

## TL;DR

This study uses transcriptomic data and machine learning to uncover interactions between oligodendrocytes and immune cells in multiple sclerosis, revealing potential therapeutic targets.

## Contribution

The study identifies lineage switching in oligodendrocytes and novel molecular interactions in MS using integrative transcriptomic and machine learning approaches.

## Key findings

- Increased Pre-OPCs and newly formed oligodendrocytes were found in normal appearing white matter in MS.
- Reduced SIRPA-CD47 interaction in MS lesions may hinder microglial phagocytosis of oligodendrocytes.
- Enhanced CD74-MIF signaling in lesions may cause microglial retention around oligodendrocytes.

## Abstract

Integrative analysis of single-nucleus RNA sequencing with machine learning and cell communication analysis reveals molecular crosstalk between oligodendrocytes and immune cells in multiple sclerosis, identifying potential therapeutic targets.

Multiple sclerosis (MS) is a chronic disease of the central nervous system. The occurrence of MS is a phased process while its cause is still unclear. Here, by combining white matter single-nucleus transcriptomic datasets from MS and control samples, we found molecular crosstalk between oligodendrocytes (OLs) and immune cells involved in MS pathology. Using a machine learning approach, we identified oligodendrocyte precursor cells (OPCs) and OL subtypes at various developmental stages. We highlighted their unique molecular characteristics and analyzed their distribution throughout development, adulthood, and in different regions impacted by MS. We also found an increased number of Pre-OPCs and newly formed oligodendrocytes (NFOLs) in normal appearing white matter (NAWM), which were scarcely detected in MS lesions. By cell communication analysis and in vitro coculture, we found the interaction between SIRPA on microglia and CD47 on stressed oligodendrocytes was significantly reduced in MS lesions compared with NAWM, potentially preventing microglial phagocytosis of OLs. In contrast, CD74-MIF signaling between microglia and OLs was increased in lesions, which may lead to their retention around OLs.