Anderson, David J and Kaplan, David I and Bell, Katrina M and Koutsis, Katerina and Haynes, John M and Mills, Richard J and Phelan, Dean G and Qian, Elizabeth L and Leitoguinho, Ana Rita and Arasaratnam, Deevina and Labonne, Tanya and Ng, Elizabeth S and Davis, Richard P and Casini, Simona and Passier, Robert and Hudson, James E and Porrello, Enzo R and Costa, Mauro W and Rafii, Arash and Curl, Clare L and Delbridge, Lea M and Harvey, Richard P and Oshlack, Alicia and Cheung, Michael M and Mummery, Christine L and Petrou, Stephen and Elefanty, Andrew G and Stanley, Edouard G and Elliott, David A (2018) NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network. Nature Communications, 9 (1). p. 1373. ISSN 2041-1723 (PMC OA)
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Additional Information: | This article is available for free from the PMC website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893543/ |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 15 Apr 2018 22:39 |
| Last Modified: | 28 Nov 2018 22:12 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/718 |
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