Human iPSC-based modeling of late-onset disease via progerin-induced aging.
Cell Stem Cell
; 13(6): 691-705, 2013 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-24315443
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Precursores de Proteínas
/
Envelhecimento
/
Proteínas Nucleares
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Células-Tronco Pluripotentes Induzidas
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
/
Animals
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Child
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Humans
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Middle aged
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2013
Tipo de documento:
Article