Publication details

An induced pluripotent stem cell model of hypoplastic left heart syndrome (HLHS) reveals multiple expression and functional differences in HLHS derived cardiac myocytes

Authors

JIANG Yan HABIBOLLAH Saba TILGNER Katarzyna COLLIN Joseph BÁRTA Tomáš AL-AAMA Jumana Yousuf TESAŘOVÁ Lenka HUSSAIN Rafiqul TRAFFORD Andrew KIRKWOOD Graham SERNAGOR Evelyne ELEFTHERIOU Cyril PRZYBORSKI Stefan STOJKOVIC Miodrag LAKO Majlinda KEAVNEY Bernard ARMSTRONG Lyle

Type Article in Periodical
Magazine / Source Stem cells translational medicine
MU Faculty or unit

Faculty of Informatics

Citation
Doi http://dx.doi.org/10.5966/sctm.2013-0105
Field Genetics and molecular biology
Keywords Hypoplastic left heart syndrome; induced pluripotent stem cells; cardiac myocytes; cardiac development; pluripotent stem cell differentiation
Description Hypoplastic left heart syndrome (HLHS) is a serious congenital cardiovascular malformation resulting in hypoplasia or atresia of the left ventricle, ascending aorta, aortic and mitral valves. Diminished flow through the left side of the heart is clearly a key contributor to the condition, but any myocardial susceptibility component is as yet undefined. Using recent advances in the field of induced pluripotent stem cells (iPSC), we have been able to generate an iPSC model of HLHS malformation and characterise the properties of cardiac myocytes (CM) differentiated from these and control-iPSC lines. Differentiation of HLHS-iPSC to cardiac lineages revealed changes in the expression of key cardiac markers and a lower ability to give rise to beating clusters when compared to control-iPSC and human embryonic stem cells (hESC). HLHS-iPSC derived CM show a lower level of myofibrillar organisation, persistence of an fetal gene expression pattern, changes in commitment to ventricular versus atriallineages and display different calcium transient patterns and electrophysiological responses to caffeine and beta-adrenergic antagonists when compared to hESC- and control-iPSC derived CM, suggesting that alternative mechanisms to release calcium from intracellular stores such as the inositol triphosphate receptor may exist in HLHS in addition to the ryanodine receptor thought to function in control-iPSC derived CM. Together our findings demonstrate that CM derived from an HLHS patient demonstrate a number of marker expression and functional differences to hESC/control iPSC derived CM, thus providing some evidence that cardiomyocyte-specific factors may influence the risk of HLHS.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info