Brain multiregion single-cell transcriptomics of ME/CFS

The aim of this project is to obtain a comprehensive understanding of molecular and cellular changes in ME/CFS. The researchers will examine several brain regions that might be affected in ME/CFS and link these to molecular alterations in specific cell types. They will also investigate immune changes in both the central nervous system (CNS) and the peripheral immune system.

Ultimately, the researchers aim to identify new molecular targets that could serve as biomarkers or form the basis for the development of new treatments for people with ME/CFS.

This study uses brain tissue from ME/CFS brain donors provided by the Netherlands Brain Bank. Inclusion is based on a confirmed ME/CFS diagnosis made during the patient’s lifetime by a treating physician or medical specialist. The project consists of two main components:

1. In-depth characterization of changes in gene expression in brain cells
   In the first part of the project, three brain regions that might be affected in ME/CFS, the hippocampus, frontal cortex, and hypothalamus, will be analyzed in great detail. These regions are selected because they are potentially linked to ME/CFS-related symptoms. Using single-nucleus RNA sequencing (snRNA-seq), researchers will identify changes in specific cell types and their activity patterns across these brain regions.
2. Profiling of immune compartments in ME/CFS
   Preliminary results of previous studies by the research team have shown specific changes in the microglia, which are specialized immune cells of the brain. These alterations have been observed across different brain regions in ME/CFS patients, suggesting possible alterations in both the central and peripheral immune systems.
   In this second part of the project, these relationships will be examined in greater depth and compared with findings from Dr. N. Eijkelkamp’s project on immune cells in the blood of ME/CFS patients. This comparison will help identify overlapping immune changes between the brain and peripheral blood.

Through this integrated approach, the researchers aim to identify shared molecular pathways or immune targets that could serve as biomarkers or potential therapeutic targets for ME/CFS.

This project is part of the Netherlands ME/CFS Cohort and Biobank (NMCB). NMCB is a collaboration of Dutch research institutes, medical centres, and patient organisations dedicated to the biomedical study of Myalgic Encephalomyelitis. It works in close collaboration with Dr. N. Eijkelkamp’s project, which investigates the role of myeloid immune cells in ME/CFS and how they contribute to disease symptoms.

The study involves multidisciplinary collaboration with both national and international researchers to achieve its scientific goals. Additionally, 2 Dutch ME/CFS patient organisations (MECVS Nederland and the ME/cvs Vereniging) are actively involved in the design and implementation of the research, ensuring that patient perspectives are integrated throughout the project.

The researchers expect to identify changes in the brain and in the immune system of people with ME/CFS. By providing the first comprehensive, cell-specific map of molecular changes in ME/CFS-affected brain regions, this project aims to uncover the cellular and molecular mechanisms underlying ME/CFS symptoms.

The results will contribute to a better understanding of the interplay between the central and peripheral immune systems in ME/CFS and may pave the way for future diagnostic and therapeutic advances.