The nervous system, with its intricate network of synaptic interactions, distinct cell types, and dynamic responses, remains one of the greatest mysteries of life. To fully understand and identify the cells, transcripts, and genes that control neural health and viability, researchers face the dual challenge of tackling the innate complexity of the CNS with experimental methods that may not give them the answers they need. Traditional techniques to classify neural cells rely on probing a small number of known targets, such as cell-type markers or amyloid plaques. However, using a constrained set of markers may bias analysis by obscuring cell subtypes under study, resulting in an inability to characterize the true extent of cellular diversity or identify novel markers.
Spatial gene expression profiling explores the dynamic nature of gene expression
patterns and regional gene expression alterations, and can reveal how these changes in expression may contribute to normal development, as well as developmental or neurodegenerative disorders.
Silas Maniatis and colleagues from the New York Genome Center used this spatial approach to investigate the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) (1). They examined gene expression in postmortem tissue of ALS patients and a murine model of the disease to uncover the spatiotemporal dynamics of disease progression, including significant molecular events like microglial activation, autophagy, and reactive gliosis, as well as gene regulation changes. Using this unbiased approach, they were able to quantify 11,138 genes in mouse and 9,624 genes in human spinal cord sections, identifying altered gene expression of several known ALS genes, as well as novel genes that may be involved in ALS pathology.
With the Visium Spatial Gene Expression Solution, 10x Genomics is making a way for researchers to explore the full transcriptome in anatomically defined regions of the central nervous system by combining histology and mRNA analysis. What discoveries do you hope to make with this new tool for neuroscience research?
Learn more about the applications of the Visium Solution by visiting the 10x Genomics Booth #708 at the 49th Annual Meeting of the Society for Neuroscience, Neuroscience 2019, in Chicago, IL, from October 19-23.
See you there!
- S. Maniatis, T. Äijö, S. Vickovic, C. Braine, K. Kang et al. Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis. Science. 364, 89–93 (2019).