학술논문

Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain
Document Type
article
Source
Cell. 185(20)
Subject
Biochemistry and Cell Biology
Biomedical and Clinical Sciences
Biological Sciences
Pediatric
Neurosciences
Stem Cell Research - Embryonic - Human
Stem Cell Research
Stem Cell Research - Nonembryonic - Non-Human
1.1 Normal biological development and functioning
2.1 Biological and endogenous factors
Underpinning research
Aetiology
Brain
Collagen
Endothelial Cells
Humans
Laminin
Midkine
Neovascularization
Pathologic
Neovascularization
Physiologic
Pericytes
angiogenesis
arterial endothelial cells
blood brain barrier
cortical organoids
endothelial cells
human prenatal brain development
mural cells
pericytes
smooth muscle cells
tip cells
venous and capillary endothelial cells
ventricular zone
Human prenatal brain development
Medical and Health Sciences
Developmental Biology
Biological sciences
Biomedical and clinical sciences
Language
Abstract
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.