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Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion
Jiajing Shan1,2, Ruyu Shi3, Liyuan Jiang1
1Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Iscience
|March 30, 2026
Summary
Researchers discovered a unique tip cell in mouse brains after chronic cerebral hypoperfusion, finding that apelin (Apln) signaling promotes angiogenesis and improves cognitive function in vascular dementia models.
Area of Science:
- Neuroscience
- Vascular Biology
- Cell Biology
Background:
- Vascular cognitive impairment and dementia (VCID) pathogenesis involves complex vascular injury and repair mechanisms.
- Understanding these processes is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To elucidate cellular and molecular mechanisms of vascular repair following chronic cerebral hypoperfusion.
- To investigate the role of apelin/apelin receptor (Apln/Aplnr) signaling in angiogenesis and cognitive recovery.
Main Methods:
- Single-cell RNA sequencing of mouse brains after asymmetric common carotid artery stenosis (ACAS).
- Immunostaining, immunoblotting, and endothelial cell (EC) culture experiments.
- In vivo treatment with [Pyr1]-Apelin-13 (Apln13) in ACAS mice, followed by functional and histological assessments.
Main Results:
- Identification and validation of a novel tip cell population in ECs.
- Enrichment of tip cells in angiogenesis pathways and upregulation of Apln/Aplnr signaling post-ACAS.
- Apln13 treatment enhanced EC functions, improved angiogenesis, preserved white matter integrity, and rescued cognitive deficits in ACAS mice.
- Astrocyte-tip cell crosstalk via Vegfa-Vegfr signaling was identified.
Conclusions:
- Tip cells play a significant role in brain angiogenesis following chronic cerebral hypoperfusion.
- Apln/Aplnr signaling is a key regulator of vascular repair and cognitive function.
- Targeting Apln/Aplnr signaling represents a promising therapeutic avenue for VCID.
