Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion
Jiajing Shan, Ruyu Shi, Liyuan Jiang, Connor Dufort, Wanying Miao, Ting-wei Mai, Junxuan Lyu, Julieta Barreiro, Kong Chen, Rehana K. Leak, Jun Chen, Xiaoming Hu
TL;DR
This study uses single-cell RNA sequencing to identify a new type of endothelial cell in the brain that responds to reduced blood flow and may help in developing treatments for vascular dementia.
Contribution
The discovery of a unique endothelial tip cell type and the role of apelin signaling in angiogenesis after chronic cerebral hypoperfusion.
Findings
A unique endothelial tip cell type was identified and linked to angiogenesis through Apln/Aplnr signaling.
Apln13 treatment improved angiogenesis, white matter integrity, and cognitive function in mice with chronic hypoperfusion.
Astrocyte-tip cell communication via Vegfa-Vegfr interactions was highlighted as a key mechanism.
Abstract
Elucidating the mechanisms underlying vascular injury and repair may guide development of therapies against vascular cognitive impairment and dementia (VD). We employed single-cell RNA sequencing to map cell populations and explore vascular responses in mouse brains collected 42 days after asymmetric common carotid artery stenosis (ACAS)-induced chronic cerebral hypoperfusion. A unique tip cell type was identified among endothelial cell (EC) clusters and validated by immunostaining. Gene Ontology analyses suggested tip cell enrichment in angiogenesis and the involvement of Apln/Aplnr signaling. Immunoblotting confirmed an increase in apelin (Apln) protein after ACAS. In EC cultures, [Pyr1]-Apelin-13 (Apln13), a selective endogenous apelin receptor agonist, enhanced EC proliferation, migration, and tube formation. Treatment with Apln13 also improved angiogenesis, white matter integrity,…
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Taxonomy
TopicsNeurological Disease Mechanisms and Treatments · Neuroinflammation and Neurodegeneration Mechanisms · Barrier Structure and Function Studies