title: SMA Human iPSC-Derived Motor Neurons Show Perturbed Differentiation and Reduced miR-335-5p Expression.
abstract: Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by mutations in the Survival Motor Neuron 1 gene, resulting in very low levels of functional Survival of Motor Neuron (SMN) protein. SMA human induced Pluripotent Stem Cells (hiPSCs) represent a useful and valid model for the study of the disorder, as they provide in vitro the target cells. MicroRNAs (miRNAs) are often reported as playing a key role in regulating neuronal differentiation and fate specification. In this study SMA hiPSCs have been differentiated towards early motor neurons and their molecular and immunocytochemical profile were compared to those of wild type cells. Cell cycle proliferation was also evaluated by fluorescence-activated cell sorting (FACS). SMA hiPSCs showed an increased proliferation rate and also higher levels of stem cell markers. Moreover; when differentiated towards early motor neurons they expressed lower levels of NCAM and MN specific markers. The expression of miR-335-5p; already identified to control self-renewal or differentiation of mouse embryonic stem cells (mESCs); resulted to be reduced during the early steps of differentiation of SMA hiPSCs compared to wild type cells. These results suggest that we should speculate a role of this miRNA both in stemness characteristic and in differentiation efficiency of these cells.
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. 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. paola.spitalieri@uniroma2.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Spitalieri
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy. valentinatalarico@hotmail.it.
authors.forename: Rosa Valentina
authors.initials: RV
authors.lastname: Talarico
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit&#224;, 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. 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; D002454:Cell Differentiation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C556347:MIRN335 microRNA, human; D035683:MicroRNAs
keywords: SMA; early motor neuron; hiPSCs; miRNA