title: Altered miRNA expression is associated with neuronal fate in G93A-SOD1 ependymal stem progenitor cells.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motoneuron loss in the CNS. In G93A-SOD1 mice, motoneuron degeneration is associated with proliferative restorative attempts of ependymal stem progenitor cells (epSPCs), usually quiescent in the spinal cord. The aims of the study were to demonstrate that epSPCs isolated from the spinal cord of G93A-SOD1 mice express neurogenic potential in vitro, and thus gain a better understanding of epSPC neural differentiation properties. For this purpose, we compared the ability of epSPCs from asymptomatic and symptomatic G93A-SOD1 and WT SOD1 transgenic mice to proliferate and differentiate into neural cells. Compared to control cells, G93A-SOD1 epSPCs differentiated more into neurons than into astrocytes, whereas oligodendrocyte proportions were similar in the two populations. G93A-SOD1 neurons were small and astrocytes had an activated phenotype. Evaluation of microRNAs, specific for neural cell fate and cell-cycle regulation, in G93A-SOD1 epSPCs showed that miR-9, miR-124a, miR-19a and miR-19b were differentially expressed. Expression analysis of the predicted miRNA targets allowed identification of a functional network in which Hes1, Pten, Socs1, and Stat3 genes were important for controlling epSPC fate. Our findings demonstrate that G93A-SOD1 epSPCs are a source of multipotent cells that have neurogenic potential in vitro, and might be a useful tool to investigate the mechanisms of neural differentiation in relation to miRNA expression whose modulation might constitute new targeted therapeutic approaches to ALS.
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: stefania.marcuzzo@istituto-besta.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marcuzzo
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: dimos.kapetis@istituto-besta.it.
authors.forename: Dimos
authors.initials: D
authors.lastname: Kapetis
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: rmantegazza@istituto-besta.it.
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: fulvio.baggi@istituto-besta.it.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Baggi
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: silvia.bonanno@istituto-besta.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonanno
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: claudia.barzago@istituto-besta.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Barzago
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: paola.cavalcante@istituto-besta.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Cavalcante
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: nicole.kerleroderosbo@gmail.com.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kerlero de Rosbo
authors.affiliation: Neurology IV-Neuromuscular Diseases and Neuroimmunology Unit, Fondazione Istituto Neurologico "Carlo Besta" (INNCB), Via Celoria 11, 20133 Milan, Italy. Electronic address: pbernasconi@istituto-besta.it.
authors.forename: Pia
authors.initials: P
authors.lastname: Bernasconi
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004805:Ependyma / Q000166:cytology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D053263:Gene Regulatory Networks / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D019081:O Antigens / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013116:Spinal Cord / Q000033:anatomy & histology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D019081:O Antigens; D050814:Octamer Transcription Factor-3; D016194:Receptors, N-Methyl-D-Aspartate; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014404:Tubulin; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: Amyotrophic lateral sclerosis; Ependymal stem progenitor cell differentiation; Ependymal stem progenitor cells; Functional network; G93A-SOD1 mouse; MicroRNAs