Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients with TTN mutations

Q: What is the clinical evidence from this study?

Population: Dilated cardiomyopathy (n=2). Intervention: Induced pluripotent stem cell (iPSC) reprogramming. Primary outcome: Successful generation and characterization of patient-specific iPSC lines.

Q: What does this research mean for the field?

Human induced pluripotent stem cell lines carrying distinct heterozygous TTN nonsense mutations can be successfully generated from dilated cardiomyopathy patients while preserving pluripotency, genomic integrity, and tri-lineage differentiation capacity. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Jiawei Li; Anurendra Kumar; Yin-Tzu Chen; Yang Zhou; Victoria Nicole Parikh; Joseph C. Wu

doi:10.1016/j.scr.2026.104065

July 20, 2026Stem Cell ResearchOpen Access

Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients with TTN mutations

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Key result

Novel patient-derived iPSC lines successfully model dilated cardiomyopathy harboring distinct truncating TTN mutations.

n=2

Why the study?

Truncating TTN mutations are a leading cause of dilated cardiomyopathy, but patient-derived cellular models to investigate the mechanobiological basis are needed.

Key Points

Derive and validate patient-specific induced pluripotent stem cell lines from individuals with dilated cardiomyopathy carrying heterozygous truncating TTN variants.
Peripheral blood mononuclear cells were isolated from two female patients with dilated cardiomyopathy aged 34 (SCVIi170-A) and 54 (SCVIi171-A) and reprogrammed using non-integrating Sendai virus vectors encoding POU5F1, SOX2, KLF4, and MYC.
Lines were characterized for pluripotency marker expression (NANOG, SOX2, OCT3/4), three-germ-layer differentiation capacity, vector clearance, mycoplasma contamination, and genomic integrity using low-pass whole-genome sequencing.
Sanger sequencing confirmed heterozygous nonsense mutations in both established lines: c.77157G>A (p.Trp25719*) in SCVIi170-A and c.84819G>A (p.Trp28273*) in SCVIi171-A.
Both lines demonstrated normal copy-number profiles across every chromosome without segmental gains or losses, achieved Sendai virus clearance by passage 28 and 30, and successfully differentiated into ectoderm, mesoderm, and endoderm.

Structured PICO

P

Population

2 female patients aged 34 and 54 with dilated cardiomyopathy harboring distinct truncating TTN mutations who provided peripheral blood mononuclear cells for reprogramming.

I

Intervention

Generation of induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) using non-integrating Sendai virus vectors (POU5F1, SOX2, KLF4, MYC).

O

Outcome

Validation of iPSC pluripotency, expression of undifferentiated markers, tri-lineage differentiation capacity, genomic integrity, and clearance of reprogramming vectors.

The creation of these patient-derived iPSC lines provides a valuable in vitro platform for investigating the mechanobiological mechanisms of titin-truncation dilated cardiomyopathy.

Limitations

Low-pass whole-genome sequencing detects only copy-number aberrations and is blind to copy-number-neutral events like balanced translocations or inversions.
Low-level mosaic abnormalities present in only a minority of cells may not produce a detectable shift in bin coverage.
Balanced whole-genome ploidy changes can be masked by genome-wide normalization during copy-number profiling.

Implication

These patient-derived iPSC lines enable mechanistic DCM studies; leaves open clinical translation.

Abstract

Titin (TTN) encodes the largest protein in the human body and is essential for sarcomere assembly and muscle mechanosensation. Truncating TTN mutations are a leading cause of dilated cardiomyopathy (DCM). Here, we generated two induced pluripotent stem cell (iPSC) lines from female DCM patients, each carrying a heterozygous nonsense point mutation that produces a truncated titin protein. Both lines were reprogrammed from peripheral blood mononuclear cells (PBMCs) and characterized for expression of undifferentiated human iPSC state markers, tri-lineage differentiation capacity, and genomic integrity by copy-number analysis. These lines provide a patient-derived platform for investigating the mechanobiological basis of titin-truncation DCM in vitro.

Discussion

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Cite This Study

Li et al. (2026) studied Dilated cardiomyopathy (n=2). Induced pluripotent stem cell (iPSC) reprogramming was evaluated on Successful generation and characterization of patient-specific iPSC lines. Two induced pluripotent stem cell lines were successfully generated and characterized from peripheral blood mononuclear cells of two female dilated cardiomyopathy patients with distinct truncating TTN mutations.

synapsesocial.com/papers/6ad0fc2515427f6a8403ffbf https://doi.org/10.1016/j.scr.2026.104065

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Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients with TTN mutations

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients with TTN mutations

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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