title: A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).
abstract: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. andrealukk@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Luchetti
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. ciafre@uniroma2.it.
authors.forename: Silvia Anna
authors.initials: SA
authors.lastname: Ciafrè
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. miky.murdi@hotmail.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Murdocca
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. arianna.malgieri@gmail.com.
authors.forename: Arianna
authors.initials: A
authors.lastname: Malgieri
authors.affiliation: Gene Expression-Microarrays Laboratory, Bambino Gesù Children's Hospital-IRCCS Polo di Ricerca-V.le di San Paolo 15, 00146 Rome, Italy. andrea.masotti@opbg.net.
authors.forename: Andrea
authors.initials: A
authors.lastname: Masotti
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy. massimo.sanchez@iss.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. mariagiulia.farace@uniroma2.it.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Farace
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. novelli@med.uniroma2.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. sangiuolo@med.uniroma2.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Sangiuolo
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein
keywords: microRNAs (miRNAs); motor neurons (MNs); neural stem cells (NSCs); spinal muscular atrophy (SMA); survival motor neuron (SMN)