Using single cell RNA sequencing to delineate the cellular and subcellular mechanisms behind intracranial aneurysm formation and progression

Intracranial aneurysms (IA) are present in approximately 2-3% of the population and, when ruptured, result in potentially devastating hemorrhagic stroke. Current theories on factors that influence IA formation and rupture involve a combination of hemodynamic stress and vessel wall inflammation. Recent bulk RNA sequencing studies have validated the presence of an inflammatory response within IA walls; however, the driver cells and specific cell-to-cell interactions responsible are poorly understood. Our lab recently refined a method (termed endovascular biopsy; EB) to safely harvest endothelial cells within IA walls. In this study, I will first use single nuclei RNA sequencing on IA dome specimens to establish a baseline transcriptome for IAs at the single cell level using extracranial superficial temporal arteries (STA) as controls. I will then use single cell RNA sequencing on EB cells to compare with IA domes, with the hypothesis that the two populations will show similar gene expression patterns. Lastly, I will use bioinformatic analyses in both an exploratory and targeted fashion to identify cells responsible for IA formation, inflammation and rupture. Successful completion of this project will bring to light novel cellular mechanisms of aneurysm instability and establish EB as a viable technique for genetic analysis of patient specific aneurysms in vivo.

Principal Investigator(s)
Award Info

SNIS Young Investigator Research Grant