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Title: 
Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging
Measurement Type: 
Transcription Profiling (RNA-Seq)
Factors: 
Age, Genetic Characteristics
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. Induced pluripotent stem cell-derived midbrain dopamine neurons from a young and old donor overexpressing either GFP or Progerin.
Contact(s): 
Curator(s): 
mmerrill

Group

Citations: 
Human iPSC-based modeling of late-onset disease via progerin-induced aging.
Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, Tu EY, Mandal PK, Vera E, Shim J-won, Kriks S, et al.
Cell Stem Cell. 2013 Dec 5; 13(6):691-705. PMID: 24315443. Abstract
Download: 
Study metadata (ISA-Tab: isa_16146_777526.zip)