Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Jeffrey Zhao

PROVIDER: E-GEOD-52431 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Human iPSC-based modeling of late-onset disease via progerin-induced aging.

Miller Justine D JD Ganat Yosif M YM Kishinevsky Sarah S Bowman Robert L RL Liu Becky B Tu Edmund Y EY Mandal Pankaj K PK Vera Elsa E Shim Jae-won JW Kriks Sonja S Taldone Tony T Fusaki Noemi N Tomishima Mark J MJ Krainc Dimitri D Milner Teresa A TA Rossi Derrick J DJ Studer Lorenz L

Cell stem cell 20131201 6

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 ...[more]

PMID: 24315443

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Dataset Information

Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging

Publications

Human iPSC-based modeling of late-onset disease via progerin-induced aging.

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