2014
An induced pluripotent stem cell model of hypoplastic left heart syndrome (HLHS) reveals multiple expression and functional differences in HLHS derived cardiac myocytes
JIANG, Yan; Saba HABIBOLLAH; Katarzyna TILGNER; Joseph COLLIN; Tomáš BÁRTA et al.Základní údaje
Originální název
An induced pluripotent stem cell model of hypoplastic left heart syndrome (HLHS) reveals multiple expression and functional differences in HLHS derived cardiac myocytes
Autoři
JIANG, Yan; Saba HABIBOLLAH; Katarzyna TILGNER; Joseph COLLIN; Tomáš BÁRTA; Jumana Yousuf AL-AAMA; Lenka TESAŘOVÁ; Rafiqul HUSSAIN; Andrew TRAFFORD; Graham KIRKWOOD; Evelyne SERNAGOR; Cyril ELEFTHERIOU; Stefan PRZYBORSKI; Miodrag STOJKOVIC; Majlinda LAKO; Bernard KEAVNEY a Lyle ARMSTRONG
Vydání
Stem cells translational medicine, 2014, 2157-6564
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10601 Cell biology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 5.709
Označené pro přenos do RIV
Ano
Kód RIV
RIV/00216224:14330/14:00074816
Organizační jednotka
Fakulta informatiky
UT WoS
EID Scopus
Klíčová slova anglicky
Hypoplastic left heart syndrome; induced pluripotent stem cells; cardiac myocytes; cardiac development; pluripotent stem cell differentiation
Štítky
Změněno: 2. 3. 2018 10:08, Mgr. Lenka Tesařová, Ph.D.
Anotace
V originále
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.
Návaznosti
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