2. Academic Validation
  3. Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion

Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion

  • iScience. 2026 Mar 11;29(4):115331. doi: 10.1016/j.isci.2026.115331.
Jiajing Shan 1 2,  Ruyu Shi 3,  Liyuan Jiang 1,  Connor Dufort 1,  Wanying Miao 1,  Ting-Wei Mai 1,  Junxuan Lyu 1 2,  Julieta Barreiro 1,  Kong Chen 4,  Rehana K Leak 5,  Jun Chen 1 2,  Xiaoming Hu 1 2
Affiliations

Affiliations

  • 1 Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • 2 Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, USA.
  • 3 Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • 4 Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • 5 Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
PMID: 41907427 DOI: 10.1016/j.isci.2026.115331
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, and cognitive functions in ACAS mice. Cell-cell interaction analyses highlighted astrocyte-tip cell crosstalk via Vegfa-Vegfr interactions.

Keywords

Integrative aspects of cell biology; Transcriptomics; Vascular remodeling.

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