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Abnormal developmental trajectory and vulnerability to cardiac arrhythmias in tetralogy of Fallot with DiGeorge syndrome.

Authors :
Chan CH
Lam YY
Wong N
Geng L
Zhang J
Ahola V
Zare A
Li RA
Lanner F
Keung W
Cheung YF
Source :
Communications biology [Commun Biol] 2023 Sep 22; Vol. 6 (1), pp. 969. Date of Electronic Publication: 2023 Sep 22.
Publication Year :
2023

Abstract

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Ventricular dysfunction and cardiac arrhythmias are well-documented complications in patients with repaired TOF. Whether intrinsic abnormalities exist in TOF cardiomyocytes is unknown. We establish human induced pluripotent stem cells (hiPSCs) from TOF patients with and without DiGeorge (DG) syndrome, the latter being the most commonly associated syndromal association of TOF. TOF-DG hiPSC-derived cardiomyocytes (hiPSC-CMs) show impaired ventricular specification, downregulated cardiac gene expression and upregulated neural gene expression. Transcriptomic profiling of the in vitro cardiac progenitors reveals early bifurcation, as marked by ectopic RGS13 expression, in the trajectory of TOF-DG-hiPSC cardiac differentiation. Functional assessments further reveal increased arrhythmogenicity in TOF-DG-hiPSC-CMs. These findings are found only in the TOF-DG but not TOF-with no DG (ND) patient-derived hiPSC-CMs and cardiac progenitors (CPs), which have implications on the worse clinical outcomes of TOF-DG patients.<br /> (© 2023. Springer Nature Limited.)

Details

Language :
English
ISSN :
2399-3642
Volume :
6
Issue :
1
Database :
MEDLINE
Journal :
Communications biology
Publication Type :
Academic Journal
Accession number :
37740059
Full Text :
https://doi.org/10.1038/s42003-023-05344-6