Induced Pluripotent Stem Cells (iPSC) of Patients with Heart Diseases
The iPSCs were generated from reprogrammed human dermal fibroblasts. The fibroblasts were derived from patients with heart diseases of distinct genetic background. Controls of healthy volunteers are also available.
A: Prolonged QT interval (Long QT syndrome type 2)
B: Prolonged QT interval (Long QT syndrome type 3)
C: Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1)
A: Heterozygous mutation c.3035-3045delTCCCTCGATGC, p.Leu1012Pro (fs*55) in KCNH2 gene.
B: Patient 1: c.1604G>A in the SCN5A gene causing p.R535Q in the intracellular linker region between domains I and II (DI/DII) of the Nav1.5 channel; Patient 2: c.718G>A in the SCN5A gene causing p.V240M in the cytoplasmic loop between membrane-spanning segments four and five within the first domain (DI-S4/S5) of the Nav1.5 channel.
C: de novo heterozygous autosomal dominant p.F2483I mutation in the cardiac Ryanodine receptor type 2 gene.
A: Transposition of OCT4, SOX2, KLF4 and c-MYC (OSKM) and miRNA302/367 expression cassettes mobilized by the SB100X hyperactive transposase.
B and C: Cells were infected with a combination of pMXs-based retroviruses (Addgene, plasmid IDs: 13366, 13367, 13370, 13375) encoding the human transcription factors OCT3/4, SOX2, KLF4, and c‑MYC.
Cardiac disease research, drug and toxicity screening
A: Fatima, A., et al. (2016) Generation of human induced pluripotent stem cell line from a patient with a long QT syndrome type 2. Stem Cell Research 16: 304–307.
B: Fatima, A., et al. (2013) The disease-specific phenotype in cardiomyocytes derived from induced pluripotent stem cells of two long QT syndrome type 3 patients. PLoS One 8, e83005.
C: Fatima, A., et al. (2011) In vitro modeling of Ryanodine receptor 2 dysfunction using human induced pluripotent stem cells. Cell. Physiol. Biochem. 28: 579-592.