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Aging (Albany NY). 2013 Apr;5(4):288-303.

An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells.

Author information

1
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.

Abstract

Lipodystrophies, characterized by partial or complete loss of adipose tissue, have been associated with mutations in the lamin A gene. It remains unclear how lamin A mutants interfere with adipose tissue formation. Hutchinson-Gilford progeria syndrome (HGPS) presents the most severe form of lamin A-associated diseases, whose patients show a complete loss of subcutaneous fat. Using iPSCs reprogrammed from HGPS fibroblasts, we induced adipocyte formation from iPSC derived embryoid bodies or from iPSC derived mesenchymal stem cells. Both approaches revealed a severe lipid storage defect in HGPS cells at late differentiation stage, faithfully recapitulating HGPS patient phenotype. Expression analysis further indicated that progerin inhibited the transcription activation of PPARγ2 and C/EBPα, but had little effects on the early adipogenic regulators. Our experiments demonstrate two comparable approaches of in vitro modeling lipodystrophies with patient-specific iPSCs, and support a regulatory role of lamin A in the terminal differentiation stage of adipogenesis.

PMID:
23596277
PMCID:
PMC3651521
DOI:
10.18632/aging.100550
[Indexed for MEDLINE]
Free PMC Article

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