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.
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Authors | Zheng-Mei Xiong, Christina LaDana, Di Wu, Kan Cao |
Journal | Aging
(Aging (Albany NY))
Vol. 5
Issue 4
Pg. 288-303
(Apr 2013)
ISSN: 1945-4589 [Electronic] United States |
PMID | 23596277
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lamin Type A
- Nuclear Proteins
- Protein Precursors
- prelamin A
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Topics |
- Adipocytes
(cytology)
- Animals
- Cell Differentiation
(physiology)
- Cells, Cultured
- Gene Expression Regulation
(physiology)
- Lamin Type A
- Nuclear Proteins
(genetics, metabolism)
- Pluripotent Stem Cells
(metabolism)
- Protein Precursors
(genetics, metabolism)
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