title: An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells.
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.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Zheng-Mei
authors.initials: ZM
authors.lastname: Xiong
authors.forename: Christina
authors.initials: C
authors.lastname: LaDana
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Kan
authors.initials: K
authors.lastname: Cao
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D034904:Lamin Type A; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A