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Status |
Public on Jan 23, 2014 |
Title |
Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) sets their identity back to an embryonic age. This presents a fundamental hurdle for modeling late-onset disorders using iPSC-derived cells. We therefore developed a strategy to induce age-like features in multiple iPSC-derived lineages and tested its impact on modeling Parkinson’s disease (PD). We first describe markers that predict fibroblast donor age and observed the loss of these age-related markers following iPSC induction and re-differentiation into fibroblasts. Remarkably, age-related markers were readily induced in iPSC-derived fibroblasts or neurons following exposure to progerin including dopamine neuron-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes requiring both aging and genetic susceptibility such as frank dendrite degeneration, progressive loss of tyrosine-hydroxylase expression and enlarged mitochondria or Lewy body-precursor inclusions. Our study presents a strategy for inducing age-related cellular properties and enables the modeling of late-onset disease features.
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Overall design |
Induced pluripotent stem cell-derived midbrain dopamine neurons from a young and old donor overexpressing either GFP or Progerin.
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Contributor(s) |
Miller JD, Bowman RL, Studer L |
Citation(s) |
24315443 |
Submission date |
Nov 15, 2013 |
Last update date |
May 15, 2019 |
Contact name |
Jeffrey Zhao |
Organization name |
Memorial Sloan Kettering Cancer Center
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Department |
Genomics Core
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Street address |
1275 York Avenue
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10065 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (8)
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Relations |
BioProject |
PRJNA228920 |
SRA |
SRP033078 |