Generation of human induced pluripotent stem cell (hiPSC) lines (UKMi009-A and UKMi011-A) harboring a homozygous and heterozygous HCN4 variant from a family with inherited sinus node dysfunction (SND).

Elisabeth Krämer, Andreas Unger, Sven Dittmann, Eric Schulze-Bahr, Jassin Hamidi, Marielle Vennemann, Patrice Bouvagnet

Journal: Stem cell research 2025;86():103740

PMID: 40414080

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Abstract

HCN4, as the predominant pacemaker current (I) in mammalian hearts, encodes the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 driving spontaneous cardiac rhythmicity. Particularly expressed in sinoatrial cells, I channels are main heart rate regulators. Here, we generated two hiPSC lines from a consanguineous family with SND where the HCN4 variant was either present in heterozygous or homozygous state. Generated hiPSCs enable further cardiomyocyte cell differentiation to provide unique patient-derived SND in-vitro disease models in a gene-dose dependent manner. Both cell lines exhibited normal karyotype, cell morphology, hiPSC marker expression, and differentiation into all three germ layers, confirmed by immunofluorescence staining.

Address: Institute for Genetics of Heart Diseases (IfGH), University Hospital Münster, Münster, Germany. Electronic address: [email protected].; Institute for Genetics of Heart Diseases (IfGH), University Hospital Münster, Münster, Germany.; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute for Physiology II, University Hospital Münster, Münster, Germany.; Institute of Legal Medicine, Forensic Molecular Biology, University Hospital Münster, Münster, Germany.; CPDP, Hôpital MFME, CHU de Martinique, BP632, 97200 Fort de France, France.

DOI: 10.1016/j.scr.2025.103740

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MeSH Terms: Humans, Induced Pluripotent Stem Cells, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Homozygote, Heterozygote, Male, Sick Sinus Syndrome, Female, Muscle Proteins, Cell Differentiation, Cell Line, Pedigree, Potassium Channels, Myocytes, Cardiac