title: Generation of induced pluripotent stem cell lines from 3 distinct laminopathies bearing heterogeneous mutations in lamin A/C.
abstract: The term laminopathies defines a group of genetic disorders caused by defects in the nuclear envelope, mostly the lamins. Lamins are the main constituents of the nuclear lamina, a filamentous meshwork associated with the inner nuclear membrane that provides mechanical stability and plays important roles in processes such as transcription, DNA replication and chromatin organization. More than 300 mutations inlamin A/C have been associated with diverse clinical phenotypes, understanding the molecular basis of these diseases may provide a rationale for treating them. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient with inherited dilated cardiomiopathy and 2 patients with distinct accelerated forms of aging, atypical Werner syndrome and Hutchinson Gilford progeria, all of which are caused by mutations in lamin A/C. These cell lines were pluripotent and displayed normal nuclear membrane morphology compared to donor fibroblasts. Their differentiated progeny reproduced the disease phenotype, reinforcing the idea that they represent excellent tools for understanding the role of lamin A/C in normal physiology and the clinical diversity associated with these diseases.
authors.affiliation: Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, China.
authors.forename: Jenny C Y
authors.initials: JC
authors.lastname: Ho
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: Wing-Hon
authors.initials: WH
authors.lastname: Lai
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Huang
authors.forename: Yau-Chi
authors.initials: YC
authors.lastname: Chan
authors.forename: Xingyan
authors.initials: X
authors.lastname: Li
authors.forename: Navy L Y
authors.initials: NL
authors.lastname: Wong
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Au
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Guo
authors.forename: Jianyong
authors.initials: J
authors.lastname: Xu
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Esteban
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D034904:Lamin Type A / Q000235:genetics*; D009154:Mutation; D034881:Nuclear Lamina / Q000648:ultrastructure; D011371:Progeria / Q000235:genetics*; D014898:Werner Syndrome / Q000235:genetics*
chemical_list: D034904:Lamin Type A