cat no | 02-3002-0000
myrCell Ventricular Cardiomyocytes TTN A-band mutation
Human iPSC-derived ventricular cardiomyocytes carrying a titin (TTN) truncating variant
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Cryopreserved human iPSC-derived cardiomyocytes with a TTN A-band mutation, generated by directed differentiation, and ready for experiments in days
- Genetically matched disease model for studying TTN-associated dilated cardiomyopathy in 2D and 3D tissue
- Highly characterised to show functional synchronised beating by day 7 post-revival
Human iPSC-derived ventricular cardiomyocytes carrying a TTN A-band frameshift mutation
Immunofluorescent staining of human iPSC-derived Ventricular Cardiomyocytes TTN A-band mutation 10 days post-thawing showing expression of N-cadherin (red), α-actinin (green), with nuclei counterstained with DAPI (blue). Alpha-actinin is a key structural component of the sarcomere and its organised localisation reflects the development of the contractile apparatus. N-cadherin is an important component of cardiac adherens junctions, mediating cell–cell adhesion and contributing to the structural and functional coupling of cardiomyocytes. The TTN mutant cardiomyocytes show a disturbed sarcomeric organisation, consistent with the disease-associated phenotype. 60x magnification.
Ventricular Cardiomyocytes TTN A-band mutation express key cardiac specific markers
Immunofluorescent staining confirms cardiomyocyte identity by robust expression of α-actinin, cardiac troponin T (cTnT), and cardiac troponin I (cTnl), with additional staining for mitochondria (mtCOX2) and N-cadherin. Notably, α-actinin staining reveals disrupted sarcomeric organisation and altered sarcomere alignment in the TTN A-band mutant cardiomyocytes, demonstrating a disease-associated structural phenotype. Nuclei are counterstained with DAPI; 60x magnification.
Distinctive sarcomeric disorganisation in Ventricular Cardiomyocytes TTN A-band mutation
Immunofluorescent staining of α-actinin at 10 days post-thaw reveals robust expression in both wild-type and TTN A-band mutant Ventricular Cardiomyocytes. However, compared to the well-organised striations in the wild-type control (top row), the TTN A-band mutant cardiomyocytes (bottom row) display a disorganised sarcomeric architecture. White boxes indicate regions magnified in the right-hand panels to detail these structural differences. Scale bar: 50 μm, 40x magnification.
TTN A-band mutation impairs longitudinal contractility in 3D engineered heart muscle
Human iPSC-derived cardiomyocytes were combined with fibroblasts in a collagen hydrogel to generate wild-type (WT) and TTN A-band heterozygous mutant (TTN A-band mutant) engineered heart muscle (EHM). Tissue function was assessed over 48 days of maturation via live longitudinal video-optical tracking (myrImager), utilising automated peak finding and pole detection. The EHMs were subsequently analysed in an organ bath under defined isometric conditions for deep functional validation at the study endpoint.
Force of contraction (FOC) measurements demonstrate a progressive improvement in WT tissues over time, whereas TTN A-band mutant EHMs display a declining trend in FOC, indicating impaired contractile function (A).
In the endpoint organ bath analysis, WT EHMs demonstrate a progressive increase in force with increasing preload, consistent with a functional Frank–Starling response, whereas TTN A-band mutant EHMs show markedly reduced preload-dependent force generation (B).
Deep phenotyping of contractility at day 48 demonstrates a reduced Ca²⁺-dependent force response in TTN A-band mutant EHMs compared with WT controls, indicating impaired contractile reserve (C).
Data shown as mean ± SEM, n=8.
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