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1. Different states of stemness of glioblastoma stem cells sustain glioblastoma subtypes indicating novel clinical biomarkers and high-efficacy customized therapies

Author

Visioli, Alberto, Trivieri, Nadia, Mencarelli, Gandino, Giani, Fabrizio, Copetti, Massimiliano, Palumbo, Orazio, Pracella, Riccardo, Cariglia, Maria Grazia, Barile, Chiara, Mischitelli, Luigi, Soriano, Amata Amy, Palumbo, Pietro, Legnani, Federico, DiMeco, Francesco, Gorgoglione, Leonardo, Pesole, Graziano, Vescovi, Angelo L., and Binda, Elena

Published
2023
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2. Growth factor independence underpins a paroxysmal, aggressive Wnt5aHigh/EphA2Low phenotype in glioblastoma stem cells, conducive to experimental combinatorial therapy

Author

Trivieri, Nadia, Visioli, Alberto, Mencarelli, Gandino, Cariglia, Maria Grazia, Marongiu, Laura, Pracella, Riccardo, Giani, Fabrizio, Soriano, Amata Amy, Barile, Chiara, Cajola, Laura, Copetti, Massimiliano, Palumbo, Orazio, Legnani, Federico, DiMeco, Francesco, Gorgoglione, Leonardo, Vescovi, Angelo L., and Binda, Elena

Published
2022
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5. Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies

Author

Visioli, Alberto, Giani, Fabrizio, Trivieri, Nadia, Pracella, Riccardo, Miccinilli, Elide, Cariglia, Maria Grazia, Palumbo, Orazio, Arleo, Andrea, Dezi, Fabio, Copetti, Massimiliano, Cajola, Laura, Restelli, Silvia, Papa, Valerio, Sciuto, Antonio, Latiano, Tiziana Pia, Carella, Massimo, Amadori, Dino, Gallerani, Giulia, Ricci, Riccardo, Alfieri, Sergio, Pesole, Graziano, Vescovi, Angelo L., and Binda, Elena

Published
2019
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6. Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis

Author

Leone, Maurizio A., primary, Gelati, Maurizio, additional, Profico, Daniela C., additional, Gobbi, Claudio, additional, Pravatà, Emanuele, additional, Copetti, Massimiliano, additional, Conti, Carlo, additional, Abate, Lucrezia, additional, Amoruso, Luigi, additional, Apollo, Francesco, additional, Balzano, Rosario F., additional, Bicchi, Ilaria, additional, Carella, Massimo, additional, Ciampini, Alessandro, additional, Colosimo, Carlo, additional, Crociani, Paola, additional, D’Aloisio, Giada, additional, Di Viesti, Pietro, additional, Ferrari, Daniela, additional, Fogli, Danilo, additional, Fontana, Andrea, additional, Frondizi, Domenico, additional, Grespi, Valentina, additional, Kuhle, Jens, additional, Laborante, Antonio, additional, Lombardi, Ivan, additional, Muzi, Gianmarco, additional, Paci, Francesca, additional, Placentino, Giuliana, additional, Popolizio, Teresa, additional, Ricciolini, Claudia, additional, Sabatini, Simonetta, additional, Silveri, Giada, additional, Spera, Cristina, additional, Stephenson, Daniel, additional, Stipa, Giuseppe, additional, Tinella, Elettra, additional, Zarrelli, Michele, additional, Zecca, Chiara, additional, Ventura, Yendri, additional, D’Alessandro, Angelo, additional, Peruzzotti-Jametti, Luca, additional, Pluchino, Stefano, additional, and Vescovi, Angelo L., additional

Published
2023
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7. BRAFV600E mutation impinges on gut microbial markers defining novel biomarkers for serrated colorectal cancer effective therapies

Author

Trivieri, Nadia, Pracella, Riccardo, Cariglia, Maria Grazia, Panebianco, Concetta, Parrella, Paola, Visioli, Alberto, Giani, Fabrizio, Soriano, Amata Amy, Barile, Chiara, Canistro, Giuseppe, Latiano, Tiziana Pia, Dimitri, Lucia, Bazzocchi, Francesca, Cassano, Dario, Vescovi, Angelo L., Pazienza, Valerio, and Binda, Elena

Published
2020
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10. Supplementary Figures from Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Author

Binda, Elena, primary, Visioli, Alberto, primary, Giani, Fabrizio, primary, Trivieri, Nadia, primary, Palumbo, Orazio, primary, Restelli, Silvia, primary, Dezi, Fabio, primary, Mazza, Tommaso, primary, Fusilli, Caterina, primary, Legnani, Federico, primary, Carella, Massimo, primary, Di Meco, Francesco, primary, Duggal, Rohit, primary, and Vescovi, Angelo L., primary

Published
2023
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11. Data from Targeting APLN/APLNR Improves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma

Author

Mastrella, Giorgia, primary, Hou, Mengzhuo, primary, Li, Min, primary, Stoecklein, Veit M., primary, Zdouc, Nina, primary, Volmar, Marie N.M., primary, Miletic, Hrvoje, primary, Reinhard, Sören, primary, Herold-Mende, Christel C., primary, Kleber, Susanne, primary, Eisenhut, Katharina, primary, Gargiulo, Gaetano, primary, Synowitz, Michael, primary, Vescovi, Angelo L., primary, Harter, Patrick N., primary, Penninger, Josef M., primary, Wagner, Ernst, primary, Mittelbronn, Michel, primary, Bjerkvig, Rolf, primary, Hambardzumyan, Dolores, primary, Schüller, Ulrich, primary, Tonn, Jörg-Christian, primary, Radke, Josefine, primary, Glass, Rainer, primary, and Kälin, Roland E., primary

Published
2023
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12. Figure S5 from Targeting APLN/APLNR Improves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma

Author

Mastrella, Giorgia, primary, Hou, Mengzhuo, primary, Li, Min, primary, Stoecklein, Veit M., primary, Zdouc, Nina, primary, Volmar, Marie N.M., primary, Miletic, Hrvoje, primary, Reinhard, Sören, primary, Herold-Mende, Christel C., primary, Kleber, Susanne, primary, Eisenhut, Katharina, primary, Gargiulo, Gaetano, primary, Synowitz, Michael, primary, Vescovi, Angelo L., primary, Harter, Patrick N., primary, Penninger, Josef M., primary, Wagner, Ernst, primary, Mittelbronn, Michel, primary, Bjerkvig, Rolf, primary, Hambardzumyan, Dolores, primary, Schüller, Ulrich, primary, Tonn, Jörg-Christian, primary, Radke, Josefine, primary, Glass, Rainer, primary, and Kälin, Roland E., primary

Published
2023
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14. Supplementary Tables from Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Author

Binda, Elena, primary, Visioli, Alberto, primary, Giani, Fabrizio, primary, Trivieri, Nadia, primary, Palumbo, Orazio, primary, Restelli, Silvia, primary, Dezi, Fabio, primary, Mazza, Tommaso, primary, Fusilli, Caterina, primary, Legnani, Federico, primary, Carella, Massimo, primary, Di Meco, Francesco, primary, Duggal, Rohit, primary, and Vescovi, Angelo L., primary

Published
2023
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15. Table S1 from Targeting APLN/APLNR Improves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma

Author

Mastrella, Giorgia, primary, Hou, Mengzhuo, primary, Li, Min, primary, Stoecklein, Veit M., primary, Zdouc, Nina, primary, Volmar, Marie N.M., primary, Miletic, Hrvoje, primary, Reinhard, Sören, primary, Herold-Mende, Christel C., primary, Kleber, Susanne, primary, Eisenhut, Katharina, primary, Gargiulo, Gaetano, primary, Synowitz, Michael, primary, Vescovi, Angelo L., primary, Harter, Patrick N., primary, Penninger, Josef M., primary, Wagner, Ernst, primary, Mittelbronn, Michel, primary, Bjerkvig, Rolf, primary, Hambardzumyan, Dolores, primary, Schüller, Ulrich, primary, Tonn, Jörg-Christian, primary, Radke, Josefine, primary, Glass, Rainer, primary, and Kälin, Roland E., primary

Published
2023
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16. Supplementary Data from Targeting APLN/APLNR Improves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma

Author

Mastrella, Giorgia, primary, Hou, Mengzhuo, primary, Li, Min, primary, Stoecklein, Veit M., primary, Zdouc, Nina, primary, Volmar, Marie N.M., primary, Miletic, Hrvoje, primary, Reinhard, Sören, primary, Herold-Mende, Christel C., primary, Kleber, Susanne, primary, Eisenhut, Katharina, primary, Gargiulo, Gaetano, primary, Synowitz, Michael, primary, Vescovi, Angelo L., primary, Harter, Patrick N., primary, Penninger, Josef M., primary, Wagner, Ernst, primary, Mittelbronn, Michel, primary, Bjerkvig, Rolf, primary, Hambardzumyan, Dolores, primary, Schüller, Ulrich, primary, Tonn, Jörg-Christian, primary, Radke, Josefine, primary, Glass, Rainer, primary, and Kälin, Roland E., primary

Published
2023
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17. Supplementary Procedures from Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Author

Binda, Elena, primary, Visioli, Alberto, primary, Giani, Fabrizio, primary, Trivieri, Nadia, primary, Palumbo, Orazio, primary, Restelli, Silvia, primary, Dezi, Fabio, primary, Mazza, Tommaso, primary, Fusilli, Caterina, primary, Legnani, Federico, primary, Carella, Massimo, primary, Di Meco, Francesco, primary, Duggal, Rohit, primary, and Vescovi, Angelo L., primary

Published
2023
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18. Data from Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Author

Binda, Elena, primary, Visioli, Alberto, primary, Giani, Fabrizio, primary, Trivieri, Nadia, primary, Palumbo, Orazio, primary, Restelli, Silvia, primary, Dezi, Fabio, primary, Mazza, Tommaso, primary, Fusilli, Caterina, primary, Legnani, Federico, primary, Carella, Massimo, primary, Di Meco, Francesco, primary, Duggal, Rohit, primary, and Vescovi, Angelo L., primary

Published
2023
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20. Supplementary Methods, Figures 1-6 from Endothelial Cells Create a Stem Cell Niche in Glioblastoma by Providing NOTCH Ligands That Nurture Self-Renewal of Cancer Stem-Like Cells

Author

Zhu, Thant S., primary, Costello, Mark A., primary, Talsma, Caroline E., primary, Flack, Callie G., primary, Crowley, Jessica G., primary, Hamm, Lisa L., primary, He, Xiaobing, primary, Hervey-Jumper, Shawn L., primary, Heth, Jason A., primary, Muraszko, Karin M., primary, DiMeco, Francesco, primary, Vescovi, Angelo L., primary, and Fan, Xing, primary

Published
2023
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21. Data from Endothelial Cells Create a Stem Cell Niche in Glioblastoma by Providing NOTCH Ligands That Nurture Self-Renewal of Cancer Stem-Like Cells

Author

Zhu, Thant S., primary, Costello, Mark A., primary, Talsma, Caroline E., primary, Flack, Callie G., primary, Crowley, Jessica G., primary, Hamm, Lisa L., primary, He, Xiaobing, primary, Hervey-Jumper, Shawn L., primary, Heth, Jason A., primary, Muraszko, Karin M., primary, DiMeco, Francesco, primary, Vescovi, Angelo L., primary, and Fan, Xing, primary

Published
2023
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22. Data from Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors

Author

Yi, Joo Mi, primary, Tsai, Hsing-Chen, primary, Glöckner, Sabine C., primary, Lin, Steven, primary, Ohm, Joyce E., primary, Easwaran, Hari, primary, James, C. David, primary, Costello, Joseph F., primary, Riggins, Gregory, primary, Eberhart, Charles G., primary, Laterra, John, primary, Vescovi, Angelo L., primary, Ahuja, Nita, primary, Herman, James G., primary, Schuebel, Kornel E., primary, and Baylin, Stephen B., primary

Published
2023
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23. Supplementary Figures 1-5, Table 1, Methods and Materials from Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors

Author

Yi, Joo Mi, primary, Tsai, Hsing-Chen, primary, Glöckner, Sabine C., primary, Lin, Steven, primary, Ohm, Joyce E., primary, Easwaran, Hari, primary, James, C. David, primary, Costello, Joseph F., primary, Riggins, Gregory, primary, Eberhart, Charles G., primary, Laterra, John, primary, Vescovi, Angelo L., primary, Ahuja, Nita, primary, Herman, James G., primary, Schuebel, Kornel E., primary, and Baylin, Stephen B., primary

Published
2023
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24. Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies

Author

Rosati, Jessica, Ferrari, Daniela, Altieri, Filomena, Tardivo, Silvia, Ricciolini, Claudia, Fusilli, Caterina, Zalfa, Cristina, Profico, Daniela C., Pinos, Francesca, Bernardini, Laura, Torres, Barbara, Manni, Isabella, Piaggio, Giulia, Binda, Elena, Copetti, Massimiliano, Lamorte, Giuseppe, Mazza, Tommaso, Carella, Massimo, Gelati, Maurizio, Valente, Enza Maria, Simeone, Antonio, and Vescovi, Angelo L.

Published
2018
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26. The EphA2 Receptor Drives Self-Renewal and Tumorigenicity in Stem-like Tumor-Propagating Cells from Human Glioblastomas

Author

Binda, Elena, Visioli, Alberto, Giani, Fabrizio, Lamorte, Giuseppe, Copetti, Massimiliano, Pitter, Ken L., Huse, Jason T., Cajola, Laura, Zanetti, Nadia, DiMeco, Francesco, De Filippis, Lidia, Mangiola, Annunziato, Maira, Giulio, Anile, Carmelo, De Bonis, Pasquale, Reynolds, Brent A., Pasquale, Elena B., and Vescovi, Angelo L.

Published
2012
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28. Additional file 1 of Growth factor independence underpins a paroxysmal, aggressive Wnt5aHigh/EphA2Low phenotype in glioblastoma stem cells, conducive to experimental combinatorial therapy

Author

Trivieri, Nadia, Visioli, Alberto, Mencarelli, Gandino, Cariglia, Maria Grazia, Marongiu, Laura, Pracella, Riccardo, Giani, Fabrizio, Soriano, Amata Amy, Barile, Chiara, Cajola, Laura, Copetti, Massimiliano, Palumbo, Orazio, Legnani, Federico, DiMeco, Francesco, Gorgoglione, Leonardo, Vescovi, Angelo L., and Binda, Elena

Subjects
Data_FILES
Abstract

Additional file 1.

Published
2022
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29. Additional file 2 of Growth factor independence underpins a paroxysmal, aggressive Wnt5aHigh/EphA2Low phenotype in glioblastoma stem cells, conducive to experimental combinatorial therapy

Author

Trivieri, Nadia, Visioli, Alberto, Mencarelli, Gandino, Cariglia, Maria Grazia, Marongiu, Laura, Pracella, Riccardo, Giani, Fabrizio, Soriano, Amata Amy, Barile, Chiara, Cajola, Laura, Copetti, Massimiliano, Palumbo, Orazio, Legnani, Federico, DiMeco, Francesco, Gorgoglione, Leonardo, Vescovi, Angelo L., and Binda, Elena

Subjects
Data_FILES
Abstract

Additional file 2.

Published
2022
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32. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis

Author

Pluchino, Stefano, Quattrini, Angelo, Brambilla, Elena, Gritti, Angela, Salani, Giuliana, Dina, Giorgia, Galli, Rossella, Del Carro, Ubaldo, Amadio, Stefano, Bergami, Alessandra, Furlan, Roberto, Comi, Giancarlo, Vescovi, Angelo L., and Martino, Gianvito

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Stefano Pluchino [1]; Angelo Quattrini [2, 3]; Elena Brambilla [1]; Angela Gritti [4]; Giuliana Salani [1]; Giorgia Dina [2]; Rossella Galli [4]; Ubaldo Del Carro [3]; Stefano Amadio [3]; [...]

Published
2003
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39. Growth factor independence underpins a paroxysmal, aggressive Wnt5aHigh/EphA2Low phenotype in glioblastoma stem cells, conducive to experimental combinatorial therapy.

Author

Trivieri, Nadia, Visioli, Alberto, Mencarelli, Gandino, Cariglia, Maria Grazia, Marongiu, Laura, Pracella, Riccardo, Giani, Fabrizio, Soriano, Amata Amy, Barile, Chiara, Cajola, Laura, Copetti, Massimiliano, Palumbo, Orazio, Legnani, Federico, DiMeco, Francesco, Gorgoglione, Leonardo, Vescovi, Angelo L., and Binda, Elena

Subjects
BRAIN tumors, GROWTH factors, STEM cells, TUMOR markers, GLIOBLASTOMA multiforme, PROGNOSIS, FALSE discovery rate, PROTEIN-tyrosine kinases
Abstract

Background: Glioblastoma multiforme (GBM) is an incurable tumor, with a median survival rate of only 14–15 months. Along with heterogeneity and unregulated growth, a central matter in dealing with GBMs is cell invasiveness. Thus, improving prognosis requires finding new agents to inhibit key multiple pathways, even simultaneously. A subset of GBM stem-like cells (GSCs) may account for tumorigenicity, representing, through their pathways, the proper cellular target in the therapeutics of glioblastomas. GSCs cells are routinely enriched and expanded due to continuous exposure to specific growth factors, which might alter some of their intrinsic characteristic and hide therapeutically relevant traits. Methods: By removing exogenous growth factors stimulation, here we isolated and characterized a subset of GSCs with a "mitogen-independent" phenotype (I-GSCs) from patient's tumor specimens. Differential side-by-side comparative functional and molecular analyses were performed either in vitro or in vivo on these cells versus their classical growth factor (GF)-dependent counterpart (D-GSCs) as well as their tissue of origin. This was performed to pinpoint the inherent GSCs' critical regulators, with particular emphasis on those involved in spreading and tumorigenic potential. Transcriptomic fingerprints were pointed out by ANOVA with Benjamini-Hochberg False Discovery Rate (FDR) and association of copy number alterations or somatic mutations was determined by comparing each subgroup with a two-tailed Fisher's exact test. The combined effects of interacting in vitro and in vivo with two emerging GSCs' key regulators, such as Wnt5a and EphA2, were then predicted under in vivo experimental settings that are conducive to clinical applications. In vivo comparisons were carried out in mouse-human xenografts GBM model by a hierarchical linear model for repeated measurements and Dunnett's multiple comparison test with the distribution of survival compared by Kaplan–Meier method. Results: Here, we assessed that a subset of GSCs from high-grade gliomas is self-sufficient in the activation of regulatory growth signaling. Furthermore, while constitutively present within the same GBM tissue, these GF-independent GSCs cells were endowed with a distinctive functional and molecular repertoire, defined by highly aggressive Wnt5aHigh/EphA2Low profile, as opposed to Wnt5aLow/EphA2High expression in sibling D-GSCs. Regardless of their GBM subtype of origin, I-GSCs, are endowed with a raised in vivo tumorigenic potential than matched D-GSCs, which were fast-growing ex-vivo but less lethal and invasive in vivo. Also, the malignant I-GSCs' transcriptomic fingerprint faithfully mirrored the original tumor, bringing into evidence key regulators of invasiveness, angiogenesis and immuno-modulators, which became candidates for glioma diagnostic/prognostic markers and therapeutic targets. Particularly, simultaneously counteracting the activity of the tissue invasive mediator Wnt5a and EphA2 tyrosine kinase receptor addictively hindered GSCs' tumorigenic and invasive ability, thus increasing survival. Conclusion: We show how the preservation of a mitogen-independent phenotype in GSCs plays a central role in determining the exacerbated tumorigenic and high mobility features distinctive of GBM. The exploitation of the I-GSCs' peculiar features shown here offers new ways to identify novel, GSCs-specific effectors, whose modulation can be used in order to identify novel, potential molecular therapeutic targets. Furthermore, we show how the combined use of PepA, the anti-Wnt5a drug, and of ephrinA1-Fc to can hinder GSCs' lethality in a clinically relevant xenogeneic in vivo model thus being conducive to perspective, novel combinatorial clinical application. [ABSTRACT FROM AUTHOR]

Published
2022
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40. Additional file 1 of BRAFV600E mutation impinges on gut microbial markers defining novel biomarkers for serrated colorectal cancer effective therapies

Author

Trivieri, Nadia, Pracella, Riccardo, Cariglia, Maria Grazia, Panebianco, Concetta, Parrella, Paola, Visioli, Alberto, Giani, Fabrizio, Soriano, Amata Amy, Barile, Chiara, Canistro, Giuseppe, Latiano, Tiziana Pia, Dimitri, Lucia, Bazzocchi, Francesca, Cassano, Dario, Vescovi, Angelo L., Pazienza, Valerio, and Binda, Elena

Abstract

Additional file 1:. Supplementary methods

Published
2020
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43. The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid

Author

de Sonnaville, Sophia F A M, van Strien, Miriam E, Middeldorp, Jinte, Sluijs, Jacqueline A, van den Berge, Simone A, Moeton, Martina, Donega, Vanessa, van Berkel, Annemiek, Deering, Tasmin, De Filippis, Lidia, Vescovi, Angelo L, Aronica, Eleonora, Glass, Rainer, van de Berg, Wilma D J, Swaab, Dick F, Robe, Pierre A, Hol, Elly M, de Sonnaville, Sophia F A M, van Strien, Miriam E, Middeldorp, Jinte, Sluijs, Jacqueline A, van den Berge, Simone A, Moeton, Martina, Donega, Vanessa, van Berkel, Annemiek, Deering, Tasmin, De Filippis, Lidia, Vescovi, Angelo L, Aronica, Eleonora, Glass, Rainer, van de Berg, Wilma D J, Swaab, Dick F, Robe, Pierre A, and Hol, Elly M

Abstract

Neurogenesis continues throughout adulthood in specialized regions of the brain. One of these regions is the subventricular zone. During brain development, neurogenesis is regulated by a complex interplay of intrinsic and extrinsic cues that control stem-cell survival, renewal and cell lineage specification. Cerebrospinal fluid (CSF) is an integral part of the neurogenic niche in development as it is in direct contact with radial glial cells, and it is important in regulating proliferation and migration. Yet, the effect of CSF on neural stem cells in the subventricular zone of the adult human brain is unknown. We hypothesized a persistent stimulating effect of ventricular CSF on neural stem cells in adulthood, based on the literature, describing bulging accumulations of subventricular cells where CSF is in direct contact with the subventricular zone. Here, we show by immunohistochemistry on post-mortem adult human subventricular zone sections that neural stem cells are in close contact with CSF via protrusions through both intact and incomplete ependymal layers. We are the first to systematically quantify subventricular glial nodules denuded of ependyma and consisting of proliferating neural stem and progenitor cells, and showed that they are present from foetal age until adulthood. Neurosphere, cell motility and differentiation assays as well as analyses of RNA expression were used to assess the effects of CSF of adult humans on primary neural stem cells and a human immortalized neural stem cell line. We show that human ventricular CSF increases proliferation and decreases motility of neural stem cells. Our results also indicate that adult CSF pushes neural stem cells from a relative quiescent to a more active state and promotes neuronal over astrocytic lineage differentiation. Thus, CSF continues to stimulate neural stem cells throughout aging.

Published
2020

44. The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid

Author

de Sonnaville, S, van Strien, M, Middeldorp, J, Sluijs, J, van den Berge, S, Moeton, M, Donega, V, van Berkel, A, Deering, T, De Filippis, L, Vescovi, A, Aronica, E, Glass, R, van de Berg, W, Swaab, D, Robe, P, Hol, E, de Sonnaville, Sophia F A M, van Strien, Miriam E, Middeldorp, Jinte, Sluijs, Jacqueline A, van den Berge, Simone A, Moeton, Martina, Donega, Vanessa, van Berkel, Annemiek, Deering, Tasmin, De Filippis, Lidia, Vescovi, Angelo L, Aronica, Eleonora, Glass, Rainer, van de Berg, Wilma D J, Swaab, Dick F, Robe, Pierre A, Hol, Elly M, de Sonnaville, S, van Strien, M, Middeldorp, J, Sluijs, J, van den Berge, S, Moeton, M, Donega, V, van Berkel, A, Deering, T, De Filippis, L, Vescovi, A, Aronica, E, Glass, R, van de Berg, W, Swaab, D, Robe, P, Hol, E, de Sonnaville, Sophia F A M, van Strien, Miriam E, Middeldorp, Jinte, Sluijs, Jacqueline A, van den Berge, Simone A, Moeton, Martina, Donega, Vanessa, van Berkel, Annemiek, Deering, Tasmin, De Filippis, Lidia, Vescovi, Angelo L, Aronica, Eleonora, Glass, Rainer, van de Berg, Wilma D J, Swaab, Dick F, Robe, Pierre A, and Hol, Elly M

Abstract

Neurogenesis continues throughout adulthood in specialized regions of the brain. One of these regions is the subventricular zone. During brain development, neurogenesis is regulated by a complex interplay of intrinsic and extrinsic cues that control stem-cell survival, renewal and cell lineage specification. Cerebrospinal fluid (CSF) is an integral part of the neurogenic niche in development as it is in direct contact with radial glial cells, and it is important in regulating proliferation and migration. Yet, the effect of CSF on neural stem cells in the subventricular zone of the adult human brain is unknown. We hypothesized a persistent stimulating effect of ventricular CSF on neural stem cells in adulthood, based on the literature, describing bulging accumulations of subventricular cells where CSF is in direct contact with the subventricular zone. Here, we show by immunohistochemistry on post-mortem adult human subventricular zone sections that neural stem cells are in close contact with CSF via protrusions through both intact and incomplete ependymal layers. We are the first to systematically quantify subventricular glial nodules denuded of ependyma and consisting of proliferating neural stem and progenitor cells, and showed that they are present from foetal age until adulthood. Neurosphere, cell motility and differentiation assays as well as analyses of RNA expression were used to assess the effects of CSF of adult humans on primary neural stem cells and a human immortalized neural stem cell line. We show that human ventricular CSF increases proliferation and decreases motility of neural stem cells. Our results also indicate that adult CSF pushes neural stem cells from a relative quiescent to a more active state and promotes neuronal over astrocytic lineage differentiation. Thus, CSF continues to stimulate neural stem cells throughout aging.

Published
2020

45. The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid

Author

TN groep Hol, Brain, Pathologie, Neurochirurgie, Cancer, Translational Neuroscience, de Sonnaville, Sophia F A M, van Strien, Miriam E, Middeldorp, Jinte, Sluijs, Jacqueline A, van den Berge, Simone A, Moeton, Martina, Donega, Vanessa, van Berkel, Annemiek, Deering, Tasmin, De Filippis, Lidia, Vescovi, Angelo L, Aronica, Eleonora, Glass, Rainer, van de Berg, Wilma D J, Swaab, Dick F, Robe, Pierre A, Hol, Elly M, TN groep Hol, Brain, Pathologie, Neurochirurgie, Cancer, Translational Neuroscience, de Sonnaville, Sophia F A M, van Strien, Miriam E, Middeldorp, Jinte, Sluijs, Jacqueline A, van den Berge, Simone A, Moeton, Martina, Donega, Vanessa, van Berkel, Annemiek, Deering, Tasmin, De Filippis, Lidia, Vescovi, Angelo L, Aronica, Eleonora, Glass, Rainer, van de Berg, Wilma D J, Swaab, Dick F, Robe, Pierre A, and Hol, Elly M

Published
2020

46. Is there a neural stem cell in the mammalian forebrain?

Author

Weiss, Samuel, Reynolds, Brent A., Vescovi, Angelo L., Morshead, Cindi, Craig, Constance G., and van der Kooy, Derek

Subjects
Stem cells -- Physiological aspects, Prosencephalon -- Physiological aspects, Developmental neurology -- Analysis, Health, Psychology and mental health
Abstract

Neural precursor cells have been of interest historically as the building blocks of the embryonic CNS and, most recently, as substrates for restorative neurological approaches. The majority of previous in vitro studies of the regulation of neural-cell proliferation by polypeptide growth factors, and in vivo studies of neural lineage, argue for the presence of precursors with limited proliferative or lineage potential in the mammalian CNS. This is in contrast to renewable tissues, such as the blood or immune system, skin epithelium and epithelium of the small intestinal crypts, which contain specialized, self-renewing cells known as stem cells. However, recent in vitro and in vivo studies from our and other laboratories lead us to conclude that neural stem cells, with self-renewal and multilineage potential, are present in the embryonic through to adult mammalian forebrain.

Published
1996

48. The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid

Author

de Sonnaville, Sophia F A M, primary, van Strien, Miriam E, additional, Middeldorp, Jinte, additional, Sluijs, Jacqueline A, additional, van den Berge, Simone A, additional, Moeton, Martina, additional, Donega, Vanessa, additional, van Berkel, Annemiek, additional, Deering, Tasmin, additional, De Filippis, Lidia, additional, Vescovi, Angelo L, additional, Aronica, Eleonora, additional, Glass, Rainer, additional, van de Berg, Wilma D J, additional, Swaab, Dick F, additional, Robe, Pierre A, additional, and Hol, Elly M, additional

Published
2020
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49. AQP4 Aggregation State Is a Determinant for Glioma Cell Fate

Author

Simone, Laura, primary, Pisani, Francesco, additional, Mola, Maria G., additional, De Bellis, Manuela, additional, Merla, Giuseppe, additional, Micale, Lucia, additional, Frigeri, Antonio, additional, Vescovi, Angelo L., additional, Svelto, Maria, additional, and Nicchia, Grazia P., additional

Published
2019
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50. Targeting APLN/APLNR Improves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma

Author

Mastrella, Giorgia, primary, Hou, Mengzhuo, additional, Li, Min, additional, Stoecklein, Veit M., additional, Zdouc, Nina, additional, Volmar, Marie N.M., additional, Miletic, Hrvoje, additional, Reinhard, Sören, additional, Herold-Mende, Christel C., additional, Kleber, Susanne, additional, Eisenhut, Katharina, additional, Gargiulo, Gaetano, additional, Synowitz, Michael, additional, Vescovi, Angelo L., additional, Harter, Patrick N., additional, Penninger, Josef M., additional, Wagner, Ernst, additional, Mittelbronn, Michel, additional, Bjerkvig, Rolf, additional, Hambardzumyan, Dolores, additional, Schüller, Ulrich, additional, Tonn, Jörg-Christian, additional, Radke, Josefine, additional, Glass, Rainer, additional, and Kälin, Roland E., additional

Published
2019
Full Text
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