Exposing the glial metabolism - common link to brain damage

Project Information

LipidGlia

Grant agreement ID: 101068962

DOI

10.3030/101068962

Project terminated on 14 February 2025

EC signature date 4 October 2022

Start date 1 July 2023

End date 30 June 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 173 847,36

Coordinated by

UNIVERSITATSKLINIKUM BONN
Germany

Periodic Reporting for period 1 - LipidGlia (Exposing the glial metabolism - common link to brain damage)

Reporting period: 2023-07-01 to 2025-06-30

Summary of the context and overall objectives of the project

White matter (WM) damage is a hallmark of various neurological conditions, from multiple sclerosis to age-related cognitive decline. At the same time, obesity—a growing public health issue in Europe—exerts profound effects on the immune system, yet its impact on brain glia during demyelination remains poorly understood. This project aimed to dissect how brain injury alters glial cell states in the brain and how are these impacted by dietary factors using cutting-edge single-cell and spatial transcriptomics integrated with ultrastructural imaging. The expected impact includes advancing mechanistic understanding of WM pathology and uncovering targets for more personalized therapies in age-related neurological disorders. The methodological innovations developed also advance the broader field of neuroimmunology and serve scientific community.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the funded period, the project provided understanding of multi-modal glial cell phenotypes and remyelination in demyelinated white matter lesions, as well as impact of western diet using advanced single cell omics, spatial transcriptomics, electron microscopy and integrative omics analysis. In addition, project established innovative novel approach intergrating spatial transcriptomics, with electron microscopy and single cell RNA-Seq enabling linking molecular and structural phenotypes of single cell in their native spatial context in tissue.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project delivered a novel multimodal method, STcEM, that integrates spatial transcriptomics with electron microscopy, enabling transcriptome-level resolution of cellular ultrastructure in native brain tissue. This approach goes significantly beyond existing tools by linking for the first time transcriptional and ulstrastructural phenotypes of single cells in their native tissue context. Functionally, the study identified lipid-associated microglial states linked to injury and diet, and revealed neuro-immune niches and interactions between glial states and infiltrating Tcells, overall contributing to our understanding of neuroinflammatory mechanisms in demyelinating conditions. These findings provide a foundation for future translational work in human tissue and highlight candidate pathways for therapeutic targeting. For broader uptake, future steps may include validating markers in human samples, adapting STcEM for clinical biobanks, and integrating findings into platforms for drug discovery and biomarker development.