Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain

Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages of vascular cell maturation is lacking, especially in the prenatal human brain. Using fluorescence-activated cell sorting, single-cell transcriptomics, and hi...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2022-09, Vol.185 (20), p.3753-3769.e18
Main Authors: Crouch, Elizabeth E, Bhaduri, Aparna, Andrews, Madeline G, Cebrian-Silla, Arantxa, Diafos, Loukas N, Birrueta, Janeth Ochoa, Wedderburn-Pugh, Kaylee, Valenzuela, Edward J, Bennett, Neal K, Eze, Ugomma C, Sandoval-Espinosa, Carmen, Chen, Jiapei, Mora, Cristina, Ross, Jayden M, Howard, Clare E, Gonzalez-Granero, Susana, Lozano, Jaime Ferrer, Vento, Maximo, Haeussler, Maximilian, Paredes, Mercedes F, Nakamura, Ken, Garcia-Verdugo, Jose Manuel, Alvarez-Buylla, Arturo, Kriegstein, Arnold R, Huang, Eric J
Format: Article
Language:English
Subjects:
Brain
Collagen
Endothelial Cells
Humans
Laminin
Midkine
Neovascularization, Pathologic - pathology
Neovascularization, Physiologic - physiology
Pericytes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages of vascular cell maturation is lacking, especially in the prenatal human brain. Using fluorescence-activated cell sorting, single-cell transcriptomics, and histological and ultrastructural analyses, we show that an ensemble of endothelial and mural cell subtypes tile the brain vasculature during the second trimester. These vascular cells follow distinct developmental trajectories and utilize diverse signaling mechanisms, including collagen, laminin, and midkine, to facilitate cell-cell communication and maturation. Interestingly, our results reveal that tip cells, a subtype of endothelial cells, are highly enriched near the ventricular zone, the site of active neurogenesis. Consistent with these observations, prenatal vascular cells transplanted into cortical organoids exhibit restricted lineage potential that favors tip cells, promotes neurogenesis, and reduces cellular stress. Together, our results uncover important mechanisms into vascular maturation during this critical period of human brain development.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2022.09.004