Show simple item record

Files in this item


Item metadata

dc.contributor.authorZhao, Chen
dc.contributor.authorDevlin, Anna-Claire
dc.contributor.authorChouhan, Amit Kumar
dc.contributor.authorSelvaraj, Bhuvaneish
dc.contributor.authorStavrou, Maria
dc.contributor.authorBurr, Karen
dc.contributor.authorBrivio, Veronica
dc.contributor.authorHe, Xin
dc.contributor.authorMehta, Arpan
dc.contributor.authorStory, David
dc.contributor.authorShaw, Christopher
dc.contributor.authorDando, Owen
dc.contributor.authorHardingham, Giles
dc.contributor.authorMiles, Gareth Brian
dc.contributor.authorChandran, Siddharthan
dc.identifier.citationZhao , C , Devlin , A-C , Chouhan , A K , Selvaraj , B , Stavrou , M , Burr , K , Brivio , V , He , X , Mehta , A , Story , D , Shaw , C , Dando , O , Hardingham , G , Miles , G B & Chandran , S 2020 , ' Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology ' , Glia , vol. 68 , no. 5 , pp. 1046-1064 .
dc.identifier.otherPURE: 263919854
dc.identifier.otherPURE UUID: d550cb4d-98ab-47e6-b823-70a8f1d4f42a
dc.identifier.otherORCID: /0000-0002-8624-4625/work/66398357
dc.identifier.otherORCID: /0000-0001-8724-155X/work/66398457
dc.identifier.otherScopus: 85076785068
dc.identifier.otherWOS: 000518850800013
dc.descriptionThis work has been supported by: Motor Neurone Disease Association (Miles/Oct 2014/878-792), Euan MacDonald Centre, Motor Neurone Disease Scotland, Dementias Platform UK (DPUK)-MRC stem cell partnership, MS Society and UK Dementia Research Institute. C.Z was funded by China Scholarship Council. A.R.M. and M.S are funded by the Medical Research Council and the Motor Neurone Disease Association. They also acknowledge support from the Rowling Scholars scheme, administered by the Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.en
dc.description.abstractMutations in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS). Accumulating evidence implicates astrocytes as important non‐cell autonomous contributors to ALS pathogenesis, although the potential deleterious effects of astrocytes on the function of motor neurons remains to be determined in a completely humanized model of C9orf72 ‐mediated ALS. Here, we use a human iPSC‐based model to study the cell autonomous and non‐autonomous consequences of mutant C9orf72 expression by astrocytes. We show that mutant astrocytes both recapitulate key aspects of C9orf72 ‐related ALS pathology and, upon co‐culture, cause motor neurons to undergo a progressive loss of action potential output due to decreases in the magnitude of voltage‐activated Na+ and K+ currents. Importantly, CRISPR/Cas‐9 mediated excision of the C9orf72 repeat expansion reverses these phenotypes, confirming that the C9orf72 mutation is responsible for both cell‐autonomous astrocyte pathology and non‐cell autonomous motor neuron pathophysiology.
dc.rightsCopyright © 2019 The Authors. GLIA published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectMotor neuronen
dc.subjectNon-cell autonomousen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.titleMutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiologyen
dc.typeJournal articleen
dc.contributor.sponsorMotor Neurone Disease Associationen
dc.contributor.sponsorMotor Neurone Disease Associationen
dc.contributor.sponsorEdinburgh Universityen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.contributor.institutionUniversity of St Andrews. Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.description.statusPeer revieweden

This item appears in the following Collection(s)

Show simple item record