High-resolution mapping of the molecular and cell biology of neurodegeneration
Bart De Strooper, Patrik Verstreken
Stein Aerts, Tim Stakenborg, Peter Peumans
Research on neurodegeneration has long focused purely on neurons, the signal-transmitting cells of the brain. However, we now know that a whole range of different cells are affected, even long before the first symptoms occur. These changes ultimately lead to irreversible immunological changes and altered brain activity, causing major problems in brain function down the line.
To fully unravel the mechanisms that ultimately lead to neuronal death and clinical symptoms such as cognitive decline, we need to measure alterations in all brain cells. Single-cell transcriptomics is a powerful method to capture those changes, but because neurodegenerative disorders involve altered cellular interactions, it is also critical to examine individual cells in the context of brain tissue. Using customized chip technologies, we will increase the sensitivity and the spatial resolution of current analytic tools to detect changes in gene expression in every single cell in its specific environment in the brain. This will enable us to study, in more detail than we could ever before, how human brain cells change at disease onset and how they respond at different stages during the course of disease.
While spatial transcriptomics focuses only on gene expression, we will extend this by measuring protein and lipid components of brain cells as well. This offers the possibility for unbiased discovery of many more potential biomarkers and drug targets.
Advances in genomics and in vivo physiology allow us to explore cellular heterogeneity in unprecedented detail. Nowhere is this more important than in the brain, where cellular heterogeneity has profound effects on all aspects of normal function and behavior and also plays an important role in disease pathology.
- Davie et al. posted on biorxiv on 21 Dec 2017. A single-cell catalogue of regulatory states in the ageing Drosophila brain.
Scientists at the ‘VIB-KU Leuven Center for Brain & Disease Research’ mapped a single-cell transcriptome catalogue of the entire adult fly brain sampled across its lifespan. These findings show an extensive heterogeneity in gene regulation that is linked to ageing and specific brain functions. Such insights generated from fly brain will serve as a reference for future studies of genetic variation and disease mutations.