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.
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Authors | Justine D Miller, Yosif M Ganat, Sarah Kishinevsky, Robert L Bowman, Becky Liu, Edmund Y Tu, Pankaj K Mandal, Elsa Vera, Jae-won Shim, Sonja Kriks, Tony Taldone, Noemi Fusaki, Mark J Tomishima, Dimitri Krainc, Teresa A Milner, Derrick J Rossi, Lorenz Studer |
Journal | Cell stem cell
(Cell Stem Cell)
Vol. 13
Issue 6
Pg. 691-705
(Dec 05 2013)
ISSN: 1875-9777 [Electronic] United States |
PMID | 24315443
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers
- Lamin Type A
- Nuclear Proteins
- Protein Precursors
- prelamin A
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Topics |
- Adult
- Age of Onset
- Aged
- Aged, 80 and over
- Aging
(pathology)
- Animals
- Biomarkers
(metabolism)
- Cell Differentiation
- Cellular Reprogramming
- Cellular Senescence
- Child
- Dopaminergic Neurons
(metabolism, pathology, transplantation, ultrastructure)
- Fibroblasts
(metabolism)
- Humans
- Induced Pluripotent Stem Cells
(metabolism)
- Lamin Type A
- Mesencephalon
(pathology)
- Mice
- Middle Aged
- Models, Biological
- Nuclear Proteins
(metabolism)
- Parkinson Disease
(pathology)
- Phenotype
- Protein Precursors
(metabolism)
- Tissue Donors
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