Document Type
Article
Publication Date
4-10-2018
JAX Source
Nat Commun 2018 Apr 10; 9(1):1373
Volume
9
Issue
1
First Page
1373
Last Page
1373
ISSN
2041-1723
PMID
29636455
DOI
https://doi.org/10.1038/s41467-018-03714-x
Abstract
Congenital heart defects can be caused by mutations in genes that guide cardiac lineage formation. Here, we show deletion of NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs), results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFRα. Furthermore, NKX2-5 null cardiomyocytes have abnormal physiology, with asynchronous contractions and altered action potentials. Molecular profiling and genetic rescue experiments demonstrate that the bHLH protein HEY2 is a key mediator of NKX2-5 function during human cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network, providing tangible evidence that hESC models can decipher the complex pathways that regulate early stage human heart development. These data provide a human context for the evaluation of pathogenic mutations in congenital heart disease.Nat Commun 2018 Apr 10; 9(1):1373.
Recommended Citation
Anderson D,
Kaplan D,
Bell K,
Koutsis K,
Haynes J,
Mills R,
Phelan D,
Qian E,
Leitoguinho A,
Arasaratnam D,
Labonne T,
Ng E,
Davis R,
Casini S,
Passier R,
Hudson J,
Porrello E,
Costa M,
Rafii A,
Curl C,
Delbridge L,
Harvey R,
Oshlack A,
Cheung M,
Mummery C,
Petrou S,
Elefanty A,
Stanley E,
Elliott D.
NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network. Nat Commun 2018 Apr 10; 9(1):1373
Comments
This open access article is licensed under a Creative Commons Attribution 4.0 International License