dc.contributor.author | Serio, A | |
dc.contributor.author | Bilican, B | |
dc.contributor.author | Barmada, SJ | |
dc.contributor.author | Ando, DM | |
dc.contributor.author | Zhao, C | |
dc.contributor.author | Siller, R | |
dc.contributor.author | Burr, K | |
dc.contributor.author | Haghi, G | |
dc.contributor.author | Story, D | |
dc.contributor.author | Nishimura, AL | |
dc.contributor.author | Carrasco, MA | |
dc.contributor.author | Phatnani, HP | |
dc.contributor.author | Shum, C | |
dc.contributor.author | Wilmut, I | |
dc.contributor.author | Maniatis, T | |
dc.contributor.author | Shaw, CE | |
dc.contributor.author | Finkbeiner, S | |
dc.contributor.author | Chandran, S | |
dc.date.accessioned | 2024-01-04T15:04:49Z | |
dc.date.available | 2024-01-04T15:04:49Z | |
dc.date.issued | 2013-02-11 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93391 | |
dc.description.abstract | Glial proliferation and activation are associated with disease progression in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia. In this study, we describe a unique platform to address the question of cell autonomy in transactive response DNA-binding protein (TDP-43) proteinopathies. We generated functional astroglia from human induced pluripotent stem cells carrying an ALS-causing TDP-43 mutation and show that mutant astrocytes exhibit increased levels of TDP-43, subcellular mislocalization of TDP-43, and decreased cell survival. We then performed coculture experiments to evaluate the effects of M337V astrocytes on the survival of wild-type and M337V TDP-43 motor neurons, showing that mutant TDP-43 astrocytes do not adversely affect survival of cocultured neurons. These observations reveal a significant and previously unrecognized glial cell-autonomous pathological phenotype associated with a pathogenic mutation in TDP-43 and show that TDP-43 proteinopathies do not display an astrocyte non-cell-autonomous component in cell culture, as previously described for SOD1 ALS. This study highlights the utility of induced pluripotent stem cell-based in vitro disease models to investigate mechanisms of disease in ALS and other TDP-43 proteinopathies. | en_US |
dc.format.extent | 4697 - 4702 | |
dc.language | eng | |
dc.publisher | National Academy of Sciences | en_US |
dc.relation.ispartof | Proc Natl Acad Sci U S A | |
dc.subject | Amyotrophic Lateral Sclerosis | en_US |
dc.subject | Astrocytes | en_US |
dc.subject | Cell Line | en_US |
dc.subject | Cell Proliferation | en_US |
dc.subject | Cell Survival | en_US |
dc.subject | Coculture Techniques | en_US |
dc.subject | DNA-Binding Proteins | en_US |
dc.subject | Humans | en_US |
dc.subject | Induced Pluripotent Stem Cells | en_US |
dc.subject | Male | en_US |
dc.subject | Middle Aged | en_US |
dc.subject | Motor Neurons | en_US |
dc.subject | Mutation | en_US |
dc.title | Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1073/pnas.1300398110 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/23401527 | en_US |
pubs.issue | 12 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 110 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |