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

Cell

The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Science Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Developmental & Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA; Pathology Service 113B, San Francisco Veterans Affairs Healthcare System, San Francisco, CA 94121, USA. Electronic address:

Published: September 2022

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550196PMC
http://dx.doi.org/10.1016/j.cell.2022.09.004DOI Listing

Publication Analysis

Top Keywords

human brain
12
endothelial mural
8
prenatal human
8
brain development
8
vascular cells
8
cells
6
brain
5
ensembles endothelial
4
mural cells
4
cells promote
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!