Human endothelial cells promote a human neural stem cell type B phenotype via Notch signaling

Brenda Gutierrez (), Tzu Chia Liu, Carly Rodriguez, Oier Pastor-Alonso, Hannah Lambing, Mercedes F. Paredes and Lisa A. Flanagan ()
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Brenda Gutierrez: University of California Irvine
Tzu Chia Liu: University of California Irvine
Carly Rodriguez: University of California Irvine
Oier Pastor-Alonso: University of California San Francisco
Hannah Lambing: University of California San Francisco
Mercedes F. Paredes: University of California San Francisco
Lisa A. Flanagan: University of California Irvine

Nature Communications, 2025, vol. 16, issue 1, 1-25

Abstract: Abstract Neural stem and progenitor cell (NSPC) and vessel-forming endothelial cell (EC) communication throughout development and adulthood is vital for normal brain function. However, much remains unclear regarding coordinated regulation of these cells, particularly in humans. We find that contact with hECs increases hNSPC type B cells, which are GFAP-expressing adult NSPCs in the subventricular zone (SVZ), leading to generation of a human type B single-cell RNA sequencing (scRNAseq) dataset. Differential gene expression demonstrates an increase in Notch downstream mediators in type B hNSPCs after hEC contact. Blocking hNSPC Notch signaling, and reducing hEC expression of the Notch ligand DLL4, abrogates the effect of hECs on type B hNSPCs. We identify S100A6 and LeX as human type B cell markers, and analysis of the postnatal human SVZ confirms co-expression of GFAP, SOX2, S100A6, LeX and PROM1 in type B cells. Sites of contact are identified between type B hNSPCs and vasculature in the SVZ, providing evidence of human type B cell contact with hECs in the postnatal human brain. Thus, hEC contact promotes human type B cells via Notch signaling and these cells are in contact in stem cell niches in the human brain.

Date: 2025
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DOI: 10.1038/s41467-025-60194-6

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