Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity
2017
Azim, Kasum | Angonin, Diane | Marcy, Guillaume | Pieropan, Francesca | Rivera, Andrea | Donega, Vanessa | Cantù, Claudio | Williams, Gareth | Berninger, Benedikt | Butt, Arthur, M | Raineteau, Olivier | Brain Research Institute [Zurich, Suisse] ; Universität Zürich [Zürich] = University of Zurich (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich) | Adult Neurogenesis and Cellular Reprogramming [Mayence, Allemagne] ; Institute of Physiological Chemistry [Mayence, Allemagne] ; University Medical Centre [Mayence, Allemagne] ; Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)-Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)-University Medical Centre [Mayence, Allemagne] ; Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)-Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU) | Focus Program Translational Neuroscience [Mayence, Allemagne] ; Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU) | Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | School of Pharmacy and Biomedical Sciences [Portsmouth, Royaume-Uni] ; University of Portsmouth | Institute of Molecular Life Sciences [Zurich, Suisse] (IMLS) ; Universität Zürich [Zürich] = University of Zurich (UZH) | Wolfson Centre for Age-Related Diseases [Londres, Royaume-Uni] ; Guy's Campus [Londres, Royaume-Uni] ; King‘s College London-King‘s College London | Biotechnology and Biological Sciences Research Council (BBSRC) http://www.bbsrc.ac.uk/ (grant number BB/M029379/1). Funding to AB lab. Multiple Sclerosis Society of UK https://www.mssociety.org.uk/ms-research/for-researchers (grant number 40). Funding to AB lab. Investissements d'Avenir/French National Research Agency (ANR) http://www.agence-nationale-recherche.fr/ (grant number ANR-11-IDEX-0007). Program "Investissements d'Avenir" to OR lab. Swiss National Science Foundation (SNF) http://www.nrp63.ch/en (grant number 406340_128291). SNF project grant NRP63 to OR lab. Swiss National Science Foundation (SNF) http://www.snf.ch/en/funding/careers/advanced-postdoc-mobility/Pages/default.aspx (grant number P300P3_154614). Advanced Post-doc mobility fellowship to KA. | ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011)
International audience
Show more [+] Less [-]English. Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs) and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP), to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.
Show more [+] Less [-]Bibliographic information
This bibliographic record has been provided by Institut national de la recherche agronomique