Research Paper Volume 5, Issue 4 pp 288—303
An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells
- 1 Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA
Received: March 25, 2013 Accepted: April 10, 2013 Published: April 14, 2013
https://doi.org/10.18632/aging.100550How to Cite
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.