dc.contributor.author | Shaw, Christopher E. | |
dc.contributor.author | Chandran, Siddharthan | |
dc.contributor.author | Bilican, B. | |
dc.contributor.author | Serio, A. | |
dc.contributor.author | Barmada, S. J. | |
dc.contributor.author | Nishimura, A. L. | |
dc.contributor.author | Sullivan, G. J. | |
dc.contributor.author | Carrasco, M. | |
dc.contributor.author | Phatnani, P. | |
dc.contributor.author | Friedman, Brad A. | |
dc.contributor.author | Puddifoot, C. A. | |
dc.contributor.author | Story, D. | |
dc.contributor.author | Fletcher, J. | |
dc.contributor.author | Park, I. H. | |
dc.contributor.author | Daley, George Quentin | |
dc.contributor.author | Wyllie, D. J. A. | |
dc.contributor.author | Hardingham, G. E. | |
dc.contributor.author | Finkbeiner, S. | |
dc.contributor.author | Wilmut, I. | |
dc.contributor.author | Finkbeiner, S. | |
dc.contributor.author | Maniatis, Thomas P. | |
dc.date.accessioned | 2012-03-01T15:13:12Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Bilican, B., A. Serio, S. J. Barmada, A. L. Nishimura, G. J. Sullivan, M. Carrasco, H. P. Phatnani et alia. Forthcoming. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal specific vulnerability. Proceedings of the National Academy of Sciences 109. | en_US |
dc.identifier.issn | 1091-6490 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:8296379 | |
dc.description.abstract | Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a sub-group of frontotemporal lobar degeneration (FTLD-TDP). Identification of TARDBP mutations in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts using induced pluripotent stem cells (iPSC). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation, and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent- resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the phosphoinositide 3-kinase pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening. | en_US |
dc.description.sponsorship | Molecular and Cellular Biology | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | National Academy of Sciences | en_US |
dc.relation.isversionof | 10.1073/pnas.1202922109 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326463/ | en_US |
dash.license | META_ONLY | |
dc.title | Mutant Induced Pluripotent Stem Cell Lines Recapitulate Aspects of TDP-43 Proteinopathies and Reveal Specific Vulnerability | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Accepted Manuscript | en_US |
dc.relation.journal | Proceedings of the National Academy of Sciences | en_US |
dash.depositing.author | Maniatis, Thomas P. | |
dash.embargo.until | 10000-01-01 | |
dash.waiver | 2012-02-29 | |
dc.identifier.doi | 10.1073/pnas.1202922109 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Daley, George | |
dash.contributor.affiliated | Maniatis, Thomas | |