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

Autor: Chan CH; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Lam YY; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Wong N; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Geng L; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Zhang J; Ming Wai Lau Centre for Reparative Medicine, Hong Kong node, Karolinska Institutet, Units 608-613 Building 15 Science Park, Hong Kong, China., Ahola V; Ming Wai Lau Centre for Reparative Medicine, Hong Kong node, Karolinska Institutet, Units 608-613 Building 15 Science Park, Hong Kong, China., Zare A; Ming Wai Lau Centre for Reparative Medicine, Hong Kong node, Karolinska Institutet, Units 608-613 Building 15 Science Park, Hong Kong, China., Li RA; Ming Wai Lau Centre for Reparative Medicine, Hong Kong node, Karolinska Institutet, Units 608-613 Building 15 Science Park, Hong Kong, China.; Dr. Li Dak-Sum Research Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong, China., Lanner F; Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet, Solnavagen 9, 17165, Stockholm, Sweden.; Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.; Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden., Keung W; Dr. Li Dak-Sum Research Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong, China., Cheung YF; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. xfcheung@hku.hk.; Ming Wai Lau Centre for Reparative Medicine, Hong Kong node, Karolinska Institutet, Units 608-613 Building 15 Science Park, Hong Kong, China. xfcheung@hku.hk.; Dr. Li Dak-Sum Research Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong, China. xfcheung@hku.hk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Sep 22; Vol. 6 (1), pp. 969. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1038/s42003-023-05344-6
Abstrakt: 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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