{
  "abstract": "Background: Myocardial infarction (MI) causes irreversible cardiomyocyte loss and adverse ventricular remodeling because of the limited regenerative capacity of adult cardiomyocytes. Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) represent a promising strategy for myocardial repair, but their therapeutic efficacy is limited by incomplete maturation and insufficient functional integration. This study investigated whether nuclear factor I A (Nfia) enhances PSC-CM-mediated cardiac repair and explored its downstream mechanism.\n\nMethods: Public single-cell RNA sequencing (scRNA-seq) data from male post-MI mouse hearts and a mouse PSC-CM differentiation dataset were analyzed to characterize post-infarction remodeling and screen candidate transcriptional regulators. Mouse PSCs/PSC-CMs were modified by lentiviral Nfia overexpression and troponin C (TnC) silencing and evaluated by quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, immunofluorescence, calcium transient analysis, dual-luciferase reporter assays, and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR). Engineered PSCs were transplanted into 10-week-old male C57BL/6N mice after MI induction by left anterior descending coronary artery ligation. Sham, MI, control PSC, Nfia-overexpressing PSC, and TnC-silenced rescue groups were used to assess cardiac function, fibrosis, cardiomyocyte hypertrophy, and lineage marker expression.\n\nResults: Post-MI cardiac tissue exhibited sustained cellular remodeling, fibrotic activation, and impaired endogenous cardiomyocyte recovery, supporting the need for PSC-CM-based repair. Nfia was identified as a candidate regulator during PSC-CM differentiation. Nfia overexpression enhanced cardiomyogenic marker expression, sarcomere organization, and calcium-handling capacity in PSC-CMs. Mechanistically, Nfia directly bound to the TnC promoter and activated TnC transcription. In vivo, transplantation of Nfia-overexpressing PSCs improved left ventricular function and attenuated adverse remodeling after MI, whereas TnC silencing weakened these reparative effects.\n\nConclusions: Nfia enhances the maturation and reparative capacity of PSC-CMs, at least in part by activating TnC transcription. The Nfia-TnC regulatory axis may provide a potential strategy to improve stem cell-based myocardial repair after MI.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, Affiliated Hospital of Yangzhou University, Yangzhou University, Institute of Cardiovascular Disease, Yangzhou, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chan Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiarui Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaochen Yuan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3ffkc1nw2zc0h.bib",
  "cited_by": 0,
  "doi": "10.21037/cdt-2026-0162",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735864/",
  "id": "3ffkc1nw2zc0h",
  "issns": [
    "2223-3652",
    "2223-3660"
  ],
  "landing_url": "https://doi.org/10.21037/cdt-2026-0162",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Pluripotent Stem Cells Research"
    ]
  ],
  "openalex": "W7223344675",
  "pdf_url": null,
  "pmcid": "PMC13735864",
  "pmid": "42991007",
  "published": "2026-09-29",
  "publisher": "AME Publications",
  "ris": "https://research.draconitic.com/paper/3ffkc1nw2zc0h.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:27Z",
      "native_id": "PMC13735864",
      "source": "pmc",
      "url": "https://doi.org/10.21037/cdt-2026-0162"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Pluripotent Stem Cells Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Nfia-mediated troponin C activation enhances pluripotent stem cell-derived cardiomyocyte function and improves cardiac remodeling after myocardial infarction",
  "title_text": "Nfia-mediated troponin C activation enhances pluripotent stem cell-derived cardiomyocyte function and improves cardiac remodeling after myocardial infarction",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:27Z",
  "url": "https://research.draconitic.com/paper/3ffkc1nw2zc0h",
  "venue": "Cardiovascular Diagnosis and Therapy",
  "versions": []
}