INSP-12. Molecular architecture of the human brain and brain cancer

Abstract

Abstract Single-cell gene expression analysis has revolutionized biomedical research, leading to comprehensive atlases of human tissues, insights into development and homeostasis and allowed highly multiplexed perturbations with cell type specificity. Here, I present our comprehensive single-cell atlas of the human nervous system, both in development and in the adult. We describe unexpected regional diversity among human glial cell types, with implications for regions-specific glial brain disease. However, in single-cell analysis, spatial context is lost, complicating the analysis of cell-cell interactions, spatial gradients and patterns of cell distribution. Spatial methods of gene expression analysis have therefore increased in importance, and are currently a very active are of research and development. We have developed a scalable and highly multiplexed method of spatial gene expression analysis based on electrophoretic capture of mRNA. I showcase its throughput and robustness by presenting complete spatial atlases of the adult mouse brain, as well as the whole developing human head at 7 weeks post-conception. Furthermore, I will discuss our ongoing work to apply these methods to human glioblastoma in order to reveal the spatial architecture of this devastating tumor.