UC Irvine

Neural stem and progenitor cells (NSPCs) and endothelial cells (ECs) are in close contact during development and throughout adulthood. Their communication is vital for proper brain development and the maintenance of adult neural stem cell niches. However, there is a lack of knowledge regarding the cross-talk between human NSPCs (hNSPCs) and human ECs (hECs). In this work, we utilize 2-dimensional and 3-dimensional co-cultures to understand how hECs regulate hNSPCs and how hNSPCs impact hECs and vessel formation. Using immunostaining along with single cell RNA sequencing (scRNAseq), we found hEC contact promotes an increase in type B hNSPCs, which are stem cells of the adult brain, via Notch signaling. In addition, hEC contact decreases hNSPC astrocytic differentiation and proliferation. Focusing on the opposite direction of signaling, we found hNSPCs stimulate vessel formation via secreted material including extracellular vesicles (EVs). We identified additional potential vessel-promoting factors expressed by human NSPCs and not mouse NSPCs as well as factors up-regulated by hNSPCs after hEC contact. Lastly, we studied the role of N-glycosylation in brain development using Magt5 null mice, which lack a key enzyme involved in N-glycan branching, and found Mgat5 null mice display increased neuronal differentiation and depletion of the NSPC pool. This work provides a better understanding of NSPC function, including how their proliferation and differentiation are controlled and how they interact with other cells in the niche, such as ECs.