Abstract 5
Category: Basic Science
At the end of the session, participants will be able to:
- To understand the spectrum of changes of the extracellular matrix in multiple sclerosis and glioblastoma
- To gain an appreciation for the spatial heterogeneity of extracellular matrix changes in injury
COI Disclosure:
None to disclose.
Presenter
Erin Stephenson is a PGY-3 in Neuropathology at the University of Calgary, where she also completed her MD and PhD. Her research interests include neuroinflammation and the extracellular matrix
Authors
Erin L. Stephenson
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada
Target Audience:
Pathologists, Residents, Medical Students
Other – Write In (Required): Researchers
CanMEDS:
Medical Expert (the integrating role)
Scholar
Recent advances in spatial transcriptomics of the extracellular matrix
Abstract
The extracellular matrix (ECM) of the central nervous system (CNS) is an interconnected network of proteins and polysaccharides with critical roles in maintaining brain homeostasis and modulating responses to injury. In neurological diseases, alterations of the ECM can be beneficial or detrimental depending on the constellation of changes. However, there is a lack of data investigating how ECM members change in relation to each other or the relevance of location following injury. The purpose of this research was to investigate how the ECM is altered in multiple sclerosis and glioblastoma, and the spatial heterogeneity of ECM changes. Active and inactive demyelinated lesions from multiple sclerosis were investigated with a combination of spatial mRNA-sequencing, single-nucleus RNA sequencing, and immunohistochemistry. There were widespread changes in the ECM and distinct ECM profiles within inactive cores, lesion rims, and surrounding white matter (Int J Mol Sci 2024; 25(2):1240). Results uncovered multiple novel ECM targets, including the SPARC family, which have the capacity to affect immune cell activation. Brain parenchyma of genetically engineered mice invaded by glioblastoma were separated into tumour core, tumour edge, and infiltrated cortex and analysed using spatial transcriptomics. There were differentially expressed ECM genes that defined tumour regions and unique expression was associated with different tumour molecular drivers. The profound spatial changes of the ECM deserve more scrutiny to appreciate the impact on neuroinflammation, injury, and repair.