The K219T-Lamin mutation induces conduction defects through epigenetic inhibition of SCN5A in human cardiac laminopathy.
Adolescent
Adult
Cardiomyopathy, Dilated
/ genetics
Cell Line
Down-Regulation
Epigenesis, Genetic
Female
Heart Conduction System
/ pathology
Heart Transplantation
Humans
Induced Pluripotent Stem Cells
Lamin Type A
/ genetics
Male
Middle Aged
Mutation
Myocardium
/ cytology
Myocytes, Cardiac
/ pathology
NAV1.5 Voltage-Gated Sodium Channel
/ genetics
Neoplasm Proteins
Polycomb Repressive Complex 2
/ metabolism
Transcription Factors
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 05 2019
22 05 2019
Historique:
received:
04
08
2017
accepted:
06
04
2019
entrez:
24
5
2019
pubmed:
24
5
2019
medline:
25
6
2019
Statut:
epublish
Résumé
Mutations in LMNA, which encodes the nuclear proteins Lamin A/C, can cause cardiomyopathy and conduction disorders. Here, we employ induced pluripotent stem cells (iPSCs) generated from human cells carrying heterozygous K219T mutation on LMNA to develop a disease model. Cardiomyocytes differentiated from these iPSCs, and which thus carry K219T-LMNA, have altered action potential, reduced peak sodium current and diminished conduction velocity. Moreover, they have significantly downregulated Na
Identifiants
pubmed: 31118417
doi: 10.1038/s41467-019-09929-w
pii: 10.1038/s41467-019-09929-w
pmc: PMC6531493
doi:
Substances chimiques
LMNA protein, human
0
Lamin Type A
0
NAV1.5 Voltage-Gated Sodium Channel
0
Neoplasm Proteins
0
SCN5A protein, human
0
SUZ12 protein, human
0
Transcription Factors
0
Polycomb Repressive Complex 2
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
2267Subventions
Organisme : NIDDK NIH HHS
ID : U54 DK107979
Pays : United States
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