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Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells
The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialised endfeet, the significance of this interaction is not understood. In contrast, it is well established that vasculature-secre...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298702/ https://www.ncbi.nlm.nih.gov/pubmed/25283993 http://dx.doi.org/10.1038/ncb3045 |
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author | Ottone, Cristina Krusche, Benjamin Whitby, Ariadne Clements, Melanie Quadrato, Giorgia Pitulescu, Mara E. Adams, Ralf H. Parrinello, Simona |
author_facet | Ottone, Cristina Krusche, Benjamin Whitby, Ariadne Clements, Melanie Quadrato, Giorgia Pitulescu, Mara E. Adams, Ralf H. Parrinello, Simona |
author_sort | Ottone, Cristina |
collection | PubMed |
description | The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialised 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 enforces quiescence and promotes 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. |
format | Online Article Text |
id | pubmed-4298702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-42987022015-05-01 Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells Ottone, Cristina Krusche, Benjamin Whitby, Ariadne Clements, Melanie Quadrato, Giorgia Pitulescu, Mara E. Adams, Ralf H. Parrinello, Simona Nat Cell Biol Article The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialised 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 enforces quiescence and promotes 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. 2014-10-05 2014-11 /pmc/articles/PMC4298702/ /pubmed/25283993 http://dx.doi.org/10.1038/ncb3045 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Ottone, Cristina Krusche, Benjamin Whitby, Ariadne Clements, Melanie Quadrato, Giorgia Pitulescu, Mara E. Adams, Ralf H. Parrinello, Simona Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells |
title | Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells |
title_full | Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells |
title_fullStr | Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells |
title_full_unstemmed | Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells |
title_short | Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells |
title_sort | direct cell-cell contact with the vascular niche maintains quiescent neural stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298702/ https://www.ncbi.nlm.nih.gov/pubmed/25283993 http://dx.doi.org/10.1038/ncb3045 |
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