title: Dedifferentiation rescues senescence of progeria cells but only while pluripotent.
abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disease in which children develop pathologies associated with old age. HGPS is caused by a mutation in the LMNA gene, resulting in the formation of a dominant negative form of the intermediate filament, nuclear structural protein lamin A, termed progerin. Expression of progerin alters the nuclear architecture and heterochromatin, affecting cell cycle progression and genomic stability. Two groups recently reported the successful generation and characterization of induced pluripotent stem cells (iPSCs) from HGPS fibroblasts. Remarkably, progerin expression and senescence phenotypes are lost in iPSCs but not in differentiated progeny. These new HGPS iPSCs are valuable for characterizing the role of progerin in driving HGPS and aging and for screening therapeutic strategies to prevent or delay cell senescence.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 523 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA 15219, USA. niedlx@upmc.edu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Niedernhofer
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
mesh_terms: D000708:Anaplasia; D002468:Cell Physiological Phenomena; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D034904:Lamin Type A; D009687:Nuclear Proteins / Q000378:metabolism; D011371:Progeria / Q000235:genetics; D011498:Protein Precursors
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors