title: Dynamic Activity of miR-125b and miR-93 during Murine Neural Stem Cell Differentiation In Vitro and in the Subventricular Zone Neurogenic Niche.
abstract: Several microRNAs (miRNAs) that are either specifically enriched or highly expressed in neurons and glia have been described, but the identification of miRNAs modulating neural stem cell (NSC) biology remains elusive. In this study, we exploited high throughput miRNA expression profiling to identify candidate miRNAs enriched in NSC/early progenitors derived from the murine subventricular zone (SVZ). Then, we used lentiviral miRNA sensor vectors (LV.miRT) to monitor the activity of shortlisted miRNAs with cellular and temporal resolution during NSC differentiation, taking advantage of in vitro and in vivo models that recapitulate physiological neurogenesis and gliogenesis and using known neuronal- and glial-specific miRNAs as reference. The LV.miRT platform allowed us monitoring endogenous miRNA activity in low represented cell populations within a bulk culture or within the complexity of CNS tissue, with high sensitivity and specificity. In this way we validated and extended previous results on the neuronal-specific miR-124 and the astroglial-specific miR-23a. Importantly, we describe for the first time a cell type- and differentiation stage-specific modulation of miR-93 and miR-125b in SVZ-derived NSC cultures and in the SVZ neurogenic niche in vivo, suggesting key roles of these miRNAs in regulating NSC function.
authors.affiliation: San Raffaele Scientific Institute, Telethon Institute for Gene Therapy (TIGET), Milano, Italy ; Department of Experimental Medicine and Biochemical Sciences, Section of Biochemistry and Molecular Biology, University of Perugia, Perugia, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lattanzi
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gentner
authors.forename: Daniela
authors.initials: D
authors.lastname: Corno
authors.forename: Tiziano
authors.initials: T
authors.lastname: Di Tomaso
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.forename: Angela
authors.initials: A
authors.lastname: Gritti
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D020869:Gene Expression Profiling; D066298:In Vitro Techniques; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D055153:Stem Cell Niche / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; C551470:Mirn93 microRNA, mouse