Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact.

Piezo2 ischemic optic neuropathy perivascular neurons retinal ganglion cells three-dimensional vascular architecture vascular lattice formation vascular perfusions

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
06 May 2024
Historique:
received: 06 12 2022
revised: 15 02 2024
accepted: 11 04 2024
medline: 12 5 2024
pubmed: 12 5 2024
entrez: 11 5 2024
Statut: aheadofprint

Résumé

The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet. Developmental ablation of Fam19a4/Nts-RGCs led to disoriented growth of penetrating vessels near the ganglion cell layer (GCL), leading to a disorganized 3D vascular lattice. We identified enriched PIEZO2 expression in Fam19a4/Nts-RGCs. Piezo2 loss from all retinal neurons or Fam19a4/Nts-RGCs abolished the direct neurovascular contacts and phenocopied the Fam19a4/Nts-RGC ablation deficits. The defective vascular structure led to reduced capillary perfusion and sensitized the retina to ischemic insults. Furthermore, we uncovered a Piezo2-dependent perivascular granule cell subset for cerebellar vascular patterning, indicating neuronal Piezo2-dependent 3D vascular patterning in the brain.

Identifiants

DOI: 10.1016/j.cell.2024.04.010 PMID: 38733989
pubmed: 38733989
pii: S0092-8674(24)00405-7
doi: 10.1016/j.cell.2024.04.010
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.Z. and X.Y. are employees of Genentech/Roche. J.K. is listed as an inventor on Boehringer Ingelheim’s patent (AAV-BR1, #10696717).

Auteurs

Kenichi Toma (K)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Mengya Zhao (M)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Shaobo Zhang (S)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Fei Wang (F)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Hannah K Graham (HK)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Jun Zou (J)

Department of Discovery Oncology, Genentech Inc., South San Francisco, CA, USA.

Shweta Modgil (S)

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Wenhao H Shang (WH)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Nicole Y Tsai (NY)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Zhishun Cai (Z)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.

Liping Liu (L)

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Guiying Hong (G)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Arnold R Kriegstein (AR)

Department of Neurology and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.

Yang Hu (Y)

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Jakob Körbelin (J)

ENDomics Lab, Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Ruobing Zhang (R)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.

Yaping Joyce Liao (YJ)

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Tyson N Kim (TN)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.

Xin Ye (X)

Department of Discovery Oncology, Genentech Inc., South San Francisco, CA, USA. Electronic address: ye.xin@gene.com.

Xin Duan (X)

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA; Department of Physiology and Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA. Electronic address: xin.duan@ucsf.edu.

Classifications MeSH