Human iPSC-based modeling of late-onset disease via progerin-induced aging Journal Article
| Authors: | Miller, J. D.; Ganat, Y. M.; Kishinevsky, S.; Bowman, R. L.; Liu, B.; Tu, E. Y.; Mandal, P. K.; Vera, E.; Shim, J. W.; Kriks, S.; Taldone, T.; Fusaki, N.; Tomishima, M. J.; Krainc, D.; Milner, T. A.; Rossi, D. J.; Studer, L. |
| Article Title: | Human iPSC-based modeling of late-onset disease via progerin-induced aging |
| Abstract: | Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) resets their identity back to an embryonic age and, thus, presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson's disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. © 2013 Elsevier Inc. |
| Journal Title: | Cell Stem Cell |
| Volume: | 13 |
| Issue: | 6 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2013-12-05 |
| Start Page: | 691 |
| End Page: | 705 |
| Language: | English |
| DOI: | 10.1016/j.stem.2013.11.006 |
| PROVIDER: | scopus |
| PUBMED: | 24315443 |
| PMCID: | PMC4153390 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):1 -- Export Date: 2 January 2014 -- Source: Scopus |
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