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dc.contributor.authorFuller, Heidi
dc.contributor.authorMandefro, Berhan
dc.contributor.authorShirran, Sally Lorna
dc.contributor.authorGross, Andrew
dc.contributor.authorKaus, Anjoscha
dc.contributor.authorBotting, Catherine Helen
dc.contributor.authorMorris, Glen
dc.contributor.authorSareen, Dhruv
dc.identifier.citationFuller , H , Mandefro , B , Shirran , S L , Gross , A , Kaus , A , Botting , C H , Morris , G & Sareen , D 2016 , ' Spinal muscular atrophy patient iPSC-derived motor neurons have reduced expression of proteins important in neuronal development ' , Frontiers in Cellular Neuroscience , vol. 9 , 506 .
dc.identifier.otherPURE: 240466608
dc.identifier.otherPURE UUID: 49220bc7-2fe7-4ec6-90d0-6fb817b6cee7
dc.identifier.otherScopus: 84957794006
dc.identifier.otherORCID: /0000-0003-3516-3507/work/32169107
dc.identifier.otherWOS: 000368036700001
dc.descriptionThis work was supported by The RJAH Institute of Orthopaedics, UK (H.F.), The SMA Trust, UK (H.F.), Cedars-Sinai Institutional startup funds (D.S), California Institute for Regenerative Medicine Grant RT-02040 (D.S.), National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124 (D.S.), and the Wellcome Trust [grant number 094476/Z/10/Z] which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews (S.S. and C.B.). D.S. is also supported by funds from National Institute of Health (NINDS) grant U54NS091046. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.abstractSpinal muscular atrophy (SMA) is an inherited neuromuscular disease primarily characterized by degeneration of spinal motor neurons, and caused by reduced levels of the SMN protein. Previous studies to understand the proteomic consequences of reduced SMN have mostly utilized patient fibroblasts and animal models. We have derived human motor neurons from type I SMA and healthy controls by creating their induced pluripotent stem cells (iPSCs). Quantitative mass spectrometry of these cells revealed increased expression of 63 proteins in control motor neurons compared to respective fibroblasts, whereas 30 proteins were increased in SMA motor neurons versus their fibroblasts. Notably, UBA1 was significantly decreased in SMA motor neurons, supporting evidence for ubiquitin pathway defects. Subcellular distribution of UBA1 was predominantly cytoplasmic in SMA motor neurons in contrast to nuclear in control motor neurons; suggestive of neurodevelopmental abnormalities. Many of the proteins that were decreased in SMA motor neurons, including beta III-tubulin and UCHL1, were associated with neurodevelopment and differentiation. These neuron-specific consequences of SMN depletion were not evident in fibroblasts, highlighting the importance of iPSC technology. The proteomic profiles identified here provide a useful resource to explore the molecular consequences of reduced SMN in motor neurons, and for the identification of novel biomarker and therapeutic targets for SMA.
dc.relation.ispartofFrontiers in Cellular Neuroscienceen
dc.rightsCopyright © 2016 Fuller, Mandefro, Shirran, Gross, Kaus, Botting, Morris and Sareen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectSpinal muscular atrophyen
dc.subjectUbiquitin-like modifier activating enzyme 1en
dc.subjectUbiquitin carboxyl-terminal esterase L1en
dc.subjectInduced pluripotent stem cellsen
dc.subjectMotor neuronen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleSpinal muscular atrophy patient iPSC-derived motor neurons have reduced expression of proteins important in neuronal developmenten
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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