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Direct cell–cell contact with the vascular niche maintains quiescent neural stem cells
Open accessAbstract
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.
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Cites
Subventricular zone astrocytes are neural stem cells in the adult mammalian brain
Doetsch, F., Caillé, I., Lim, D. A., García-Verdugo, J. M., & Alvarez-Buylla, A. (1999) · Cell · doi:10.1016/s0092-8674(00)80783-7 · Cited by 3,898
Doetsch, F., Garcı́a-Verdugo, J. M., & Alvarez-Buylla, A. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-13-05046.1997 · Cited by 1,902
Socializing with the Neighbors
Fuchs, E., Tumbar, T., & Guasch, G. (2004) · Cell · doi:10.1016/s0092-8674(04)00255-7 · Cited by 1,719
Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells
Shen, Q., Goderie, S. K., Jin, L., Karanth, N., Sun, Y., Abramova, N., Vincent, P., Pumiglia, K., & Temple, S. (2004) · Science · doi:10.1126/science.1095505 · Cited by 1,542
Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
Wang, Y., Nakayama, M., Pitulescu, M. E., Schmidt, T. S., Bochenek, M. L., Sakakibara, A., Adams, S., Davy, A., Deutsch, U., Lüthi, U., et al. (2010) · Nature · doi:10.1038/nature09002 · Cited by 1,271
Self-citationEph-Ephrin Bidirectional Signaling in Physiology and Disease
Pasquale, E. B. (2008) · Cell · doi:10.1016/j.cell.2008.03.011 · Cited by 1,252
A specialized vascular niche for adult neural stem cells
Tavazoie, M., Van der Veken, L., Silva-Vargas, V., Louissaint, M., Colonna, L., Zaidi, B., Garcia-Verdugo, J. M., & Doetsch, F. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.025 · Cited by 1,033
Shen, Q., Wang, Y., Kokovay, E., Lin, G., Chuang, S.-M., Goderie, S. K., Roysam, B., & Temple, S. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.026 · Cited by 1,027
Mirzadeh, Z., Merkle, F. T., Soriano-Navarro, M., Garcia-Verdugo, J. M., & Alvarez-Buylla, A. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.004 · Cited by 1,015
Sherr, C. J. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89005-2 · Cited by 980
Origin of oligodendrocytes in the subventricular zone of the adult brain
Menn, B., Garcia-Verdugo, J. M., Yaschine, C., Gonzalez-Perez, O., Rowitch, D., & Alvarez-Buylla, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1299-06.2006 · Cited by 972
Organizing cell renewal in the intestine: stem cells, signals and combinatorial control
Crosnier, C., Stamataki, D., & Lewis, J. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1840 · Cited by 754
Imayoshi, I., Sakamoto, M., Yamaguchi, M., Mori, K., & Kageyama, R. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4987-09.2010 · Cited by 716
Codega, P., Silva-Vargas, V., Paul, A., Maldonado-Soto, A. R., DeLeo, A. M., Pastrana, E., & Doetsch, F. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.039 · Cited by 634
Neuronal fate determinants of adult olfactory bulb neurogenesis
Hack, M. A., Saghatelyan, A., de Chevigny, A., Pfeifer, A., Ashery-Padan, R., Lledo, P.-M., & Götz, M. (2005) · Nature Neuroscience · doi:10.1038/nn1479 · Cited by 618
Differential Notch signalling distinguishes neural stem cells from intermediate progenitors
Mizutani, K.-I., Yoon, K., Dang, L., Tokunaga, A., & Gaiano, N. (2007) · Nature · doi:10.1038/nature06090 · Cited by 521
EphB Signaling Directs Peripheral Nerve Regeneration through Sox2-Dependent Schwann Cell Sorting
Parrinello, S., Napoli, I., Ribeiro, S., Digby, P. W., Fedorova, M., Parkinson, D. B., Doddrell, R. D. S., Nakayama, M., Adams, R. H., & Lloyd, A. C. (2010) · Cell · doi:10.1016/j.cell.2010.08.039 · Cited by 493
Self-citationArchitecture and cell types of the adult subventricular zone: In search of the stem cells
Garc�a-Verdugo, J. M., Doetsch, F., Wichterle, H., Lim, D. A., & Alvarez-Buylla, A. (1998) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(199808)36:2<234::aid-neu10>3.0.co;2-e · Cited by 486
Conover, J. C., Doetsch, F., Garcia-Verdugo, J.-M., Gale, N. W., Yancopoulos, G. D., & Alvarez-Buylla, A. (2000) · Nature Neuroscience · doi:10.1038/80606 · Cited by 481
Zhu, T. S., Costello, M. A., Talsma, C. E., Flack, C. G., Crowley, J. G., Hamm, L. L., He, X., Hervey-Jumper, S. L., Heth, J. A., Muraszko, K. M., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4269 · Cited by 400
Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain
Kintner, C. (1992) · Cell · doi:10.1016/0092-8674(92)90404-z · Cited by 387
Pastrana, E., Cheng, L.-C., & Doetsch, F. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810407106 · Cited by 380
Gale, N. W., Baluk, P., Pan, L., Kwan, M., Holash, J., DeChiara, T. M., McDonald, D. M., & Yancopoulos, G. D. (2001) · Developmental Biology · doi:10.1006/dbio.2000.0112 · Cited by 363
Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis
Lim, D. A., & Alvarez-Buylla, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7526 · Cited by 362
Kokovay, E., Goderie, S., Wang, Y., Lotz, S., Lin, G., Sun, Y., Roysam, B., Shen, Q., & Temple, S. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.05.019 · Cited by 359
Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway
Miao, H., Wei, B.-R., Peehl, D. M., Li, Q., Alexandrou, T., Schelling, J. R., Rhim, J. S., Sedor, J. R., Burnett, E., & Wang, B. (2001) · Nature Cell Biology · doi:10.1038/35074604 · Cited by 358
Cell fusion-independent differentiation of neural stem cells to the endothelial lineage
Wurmser, A. E., Nakashima, K., Summers, R. G., Toni, N., D'Amour, K. A., Lie, D. C., & Gage, F. H. (2004) · Nature · doi:10.1038/nature02604 · Cited by 357
Notch in the Vertebrate Nervous System: An Old Dog with New Tricks
Pierfelice, T., Alberi, L., & Gaiano, N. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.031 · Cited by 353
Lake-Front Property: A Unique Germinal Niche by the Lateral Ventricles of the Adult Brain
Ihrie, R. A., & Álvarez-Buylla, A. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.004 · Cited by 350
Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear
Brooker, R., Hozumi, K., & Lewis, J. (2006) · Development · doi:10.1242/dev.02284 · Cited by 330
Ehm, O., Göritz, C., Covic, M., Schäffner, I., Schwarz, T. J., Karaca, E., Kempkes, B., Kremmer, E., Pfrieger, F. W., Espinosa, L., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1567-10.2010 · Cited by 318
Stem cells living with a Notch
Koch, U., Lehal, R., & Radtke, F. (2013) · Development · doi:10.1242/dev.080614 · Cited by 283
The Stem Cell Niche in Regenerative Medicine
Wagers, A. J. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.02.018 · Cited by 269
Adherent Neural Stem (NS) Cells from Fetal and Adult Forebrain
Pollard, S. M., Conti, L., Sun, Y., Goffredo, D., & Smith, A. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhj167 · Cited by 258
Hippocampal plasticity requires postsynaptic ephrinBs
Grunwald, I. C., Korte, M., Adelmann, G., Plueck, A., Kullander, K., Adams, R. H., Frotscher, M., Bonhoeffer, T., & Klein, R. (2004) · Nature Neuroscience · doi:10.1038/nn1164 · Cited by 250
Self-citationThe neurovascular link in health and disease: molecular mechanisms and therapeutic implications
Quaegebeur, A., Lange, C., & Carmeliet, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.013 · Cited by 247
Adhesion in the stem cell niche: biological roles and regulation
Chen, S., Lewallen, M., & Xie, T. (2013) · Development · doi:10.1242/dev.083139 · Cited by 245
Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone
Andreu-Agulló, C., Morante-Redolat, J. M., Delgado, A. C., & Fariñas, I. (2009) · Nature Neuroscience · doi:10.1038/nn.2437 · Cited by 218
Kokovay, E., Wang, Y., Kusek, G., Wurster, R., Lederman, P., Lowry, N., Shen, Q., & Temple, S. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.06.016 · Cited by 201
The Subventricular Zone En-face: Wholemount Staining and Ependymal Flow
Mirzadeh, Z., Doetsch, F., Sawamoto, K., Wichterle, H., & Alvarez-Buylla, A. (2010) · Journal of Visualized Experiments · doi:10.3791/1938 · Cited by 194
Collective cell migration of epithelial and mesenchymal cells
Theveneau, E., & Mayor, R. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1251-7 · Cited by 171
Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis
Calvo, C.-F., Fontaine, R. H., Soueid, J., Tammela, T., Makinen, T., Alfaro-Cervello, C., Bonnaud, F., Miguez, A., Benhaim, L., Xu, Y., et al. (2011) · Genes & Development · doi:10.1101/gad.615311 · Cited by 171
Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis
Kawaguchi, D., Furutachi, S., Kawai, H., Hozumi, K., & Gotoh, Y. (2013) · Nature Communications · doi:10.1038/ncomms2895 · Cited by 154
Phenotypic and functional characterization of adult brain neuropoiesis
Scheffler, B., Walton, N. M., Lin, D. D., Goetz, A., Enikolopov, G., Roper, S. N., & Steindler, D. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503965102 · Cited by 141
Home at Last: Neural Stem Cell Niches Defined
Miller, F. D., & Gauthier-Fisher, A. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.05.008 · Cited by 140
Diverse Roles of the Vasculature within the Neural Stem Cell Niche
Goldberg, J. S., & Hirschi, K. K. (2009) · Regenerative Medicine · doi:10.2217/rme.09.61 · Cited by 121
EphB Signaling Controls Lineage Plasticity of Adult Neural Stem Cell Niche Cells
Nomura, T., Göritz, C., Catchpole, T., Henkemeyer, M. J., & Frisén, J. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.11.009 · Cited by 99
A combined ex/in vivo assay to detect effects of exogenously added factors in neural stem cells
Ferrón, S. R., Andreu-Agulló, C., Mira, H., Sánchez‐Gómez, P., Marqués‐Torrejón, M. Á., & Fariñas, I. (2007) · Nature Protocols · doi:10.1038/nprot.2007.104 · Cited by 93
Ephrin-B2 forward signaling regulates somite patterning and neural crest cell development
Davy, A., & Soriano, P. M. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.12.028 · Cited by 90
Restricting self-renewal signals within the stem cell niche: multiple levels of control
Chen, S., Wang, S., & Xie, T. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.07.008 · Cited by 79
Mathieu, C., Sii-Felice, K., Fouchet, P., Etienne, O., Haton, C., Mabondzo, A. M., Boussin, F. D., & Mouthon, M. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.05.005 · Cited by 70
Sun, Y., Jin, H., Zhou, L., Pollard, S. M., & Smith, A. G. (2011) · Journal of Cell Science · doi:10.1242/jcs.085506 · Cited by 64
Yoshioka, N., Asou, H., Hisanaga, S., & Kawano, H. (2011) · The Journal of Comparative Neurology · doi:10.1002/cne.22788 · Cited by 16
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Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later
Bond, A. M., Ming, G.-L., & Song, H. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.003 · Cited by 791
“In the SVZ, endothelial cell expression of ephrinB2 and Jagged1 promotes NSC quiescence by suppressing cell-cycle entry and inhibiting differentiation, and loss of either gene results in NSC activation and depletion (Ottone et al., 2014).”
BackgroundNeural stem cells: origin, heterogeneity and regulation in the adult mammalian brain
Obernier, K., & Alvarez-Buylla, A. (2019) · Development · doi:10.1242/dev.156059 · Cited by 578
The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis
Lim, D. A., & Alvarez-Buylla, A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018820 · Cited by 571
Zhang, J., Muri, J., Fitzgerald, G., Gorski, T., Gianni-Barrera, R., Masschelein, E., D’Hulst, G., Gilardoni, P., Turiel, G., Fan, Z., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.004 · Cited by 533
Neurogenesis in the embryonic and adult brain: same regulators, different roles
Urbán, N., & Guillemot, F. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00396 · Cited by 493
Metadata
- Authors
- Ottone, C., Krusche, B., Whitby, A., Clements, M., Quadrato, G., Pitulescu, M. E., Adams, R. H., & Parrinello, S.
- Venue
- Nature Cell Biology
- Published
- 2014-10-05
- Volume
- 16
- Issue
- 11
- Pages
- 1045-1056
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2009953822
- Cited by
- 282
- References
- 53
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Open access
- green
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