Gutierrez Brenda, Liu Tzu Chia, Rodriguez Carly, Pastor-Alonso Oier, Lambing Hannah, Paredes Mercedes F, Flanagan Lisa A
Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA.
Sue & Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.
Nat Commun. 2025 May 30;16(1):5031. doi: 10.1038/s41467-025-60194-6.
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.
神经干细胞和祖细胞（NSPC）与血管形成内皮细胞（EC）在整个发育和成年期的通讯对于正常脑功能至关重要。然而，关于这些细胞的协调调控，尤其是在人类中，仍有许多不清楚的地方。我们发现与人类内皮细胞（hECs）接触会增加B型人类神经干细胞（hNSPCs），即脑室下区（SVZ）中表达胶质纤维酸性蛋白（GFAP）的成年神经干细胞，从而生成了一个人类B型单细胞RNA测序（scRNAseq）数据集。差异基因表达显示，hNSPCs与hECs接触后，B型hNSPCs中Notch下游介质增加。阻断hNSPC的Notch信号，并降低Notch配体DLL4的hEC表达，可消除hECs对B型hNSPCs的影响。我们将S100A6和LeX鉴定为人类B型细胞标志物，对出生后人脑SVZ的分析证实了GFAP、SOX2、S100A6、LeX和PROM1在B型细胞中的共表达。在SVZ中确定了B型hNSPCs与脉管系统之间的接触位点，为出生后人脑中B型细胞与hECs的接触提供了证据。因此，hEC接触通过Notch信号促进人类B型细胞，并且这些细胞在人类大脑的干细胞龛中存在接触。
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