title: Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells.
abstract: The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialized endfeet, the significance of this interaction is not understood. In contrast, it is well established that vasculature-secreted soluble factors promote lineage progression of committed progenitors. Here we specifically investigated the role of cell-cell contact-dependent signalling in the vascular niche. Unexpectedly, we find that direct cell-cell interactions with endothelial cells enforce quiescence and promote stem cell identity. Mechanistically, endothelial ephrinB2 and Jagged1 mediate these effects by suppressing cell-cycle entry downstream of mitogens and inducing stemness genes to jointly inhibit differentiation. In vivo, endothelial-specific ablation of either of the genes which encode these proteins, Efnb2 and Jag1 respectively, aberrantly activates quiescent stem cells, resulting in depletion. Thus, we identify the vasculature as a critical niche compartment for stem cell maintenance, furthering our understanding of how anchorage to the niche maintains stem cells within a pro-differentiative microenvironment.
authors.affiliation: Cell Interactions and Cancer Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road London W12 0NN, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ottone
authors.affiliation: Cell Interactions and Cancer Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road London W12 0NN, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Krusche
authors.affiliation: Cell Interactions and Cancer Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road London W12 0NN, UK.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Whitby
authors.affiliation: Cell Interactions and Cancer Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road London W12 0NN, UK.
authors.forename: Melanie
authors.initials: M
authors.lastname: Clements
authors.affiliation: Hertie Institute for Brain Research, University of Tuebingen, Tuebingen D-72076, Germany.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Quadrato
authors.affiliation: Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and Faculty of Medicine, University of Muenster, Muenster D-48149, Germany.
authors.forename: Mara E
authors.initials: ME
authors.lastname: Pitulescu
authors.affiliation: Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and Faculty of Medicine, University of Muenster, Muenster D-48149, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: Cell Interactions and Cancer Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road London W12 0NN, UK.
authors.forename: Simona
authors.initials: S
authors.lastname: Parrinello
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology; D036388:Ephrin-B2 / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology; D000072099:Serrate-Jagged Proteins; D055153:Stem Cell Niche / Q000235:genetics / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D036388:Ephrin-B2; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins