J 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

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

CZ.1.07/2.3.00/30.0030, interní kód MU
Název: Rozvoj lidských zdrojů pro oblast buněčné biologie
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Rozvoj lidských zdrojů pro oblast buněčné biologie, 2.3 Lidské zdroje ve výzkumu a vývoji