SINGLE-CELL TRANSCRIPTOMIC PROFILING OF THE HYPERTENSION MOUSE BRAIN

Abstract

Objective: Chronic hypertension has devastating effects on the brain, being the major cause of stroke and a leading cause of dementia. The alterations of cerebral blood vessels structure and vasoregulatory mechanisms leading by hypertension have been recognized for decades. However, the specific cellular and molecular mediators that drive these alterations remain unclear. Design and method: After 4 weeks of continuous administration of angiotensin II, we performed a single-cell transcriptomic analysis of brain cellulome. The brain cellular ecosystem in response to angiotensin II was analyzed, the network of cells that forms the mouse brain was profiled after a proinflammation stimulus that drives pathological brain vascular remodeling. Results: We analyzed the transcriptomes of 52,856 single cells (28,078 normal and 24,778 angiotensin II) derived from the brains of 10 normal and 12 angiotensin II mice, and compared all the cellular composition and transcriptomes of the whole brain cells. For all the major cell populations, we provide comprehensive datasets of genes and pathways whose transcriptional profiles change with hypertension. To reveal heterogeneity within each population, we grouped the cells into 14 classes based on the expression profile, lineage, function and anatomical organization. Of the 20718 total detected genes, 800 were significantly affected by hypertension in at least one cell type. Hypertensive- related cellular pathways and processes were also investigated, and we highlight changes in EC and EPC. Furthermore, the cellular responses to angiotensin II and the changes in intercellular communication were identified. Conclusions: These large-scale datasets provide a valuable resource for exploring the brain cellular landscape in health and after chronic cerebral vascular stress. These data provide insights into the cellular and molecular mechanisms that afford an additional discoveries of directed towards understanding the mechanisms by which hypertension disrupts cerebral blood vessels.