{
  "abstract": "Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show decreasing cell-cycle activity during prolonged culture. However, it remains unclear whether changes in cell-cycle activity occur before, after, or concurrently with transcriptional changes in cell-cycle and maturation-associated programs. Here, we combined a TNNT2-FUCCI reporter, Ki67 immunostaining, and bulk RNA sequencing to define how cell-cycle activity changes during prolonged human iPSC-cardiomyocyte culture. FUCCI and Ki67 analyses showed similar levels of cell-cycle activity at days 20 and 30 of cardiomyocyte differentiation but declined more clearly by day 40. In contrast, transcriptomic profiling revealed that canonical cell-cycle and DNA-replication programs were already reduced by day 30. The subsequent day-30-to-day-40 interval was characterized by increased expression of sarcomeric, contractile, and calcium-handling gene programs rather than a further broad loss of mitotic pathways. These findings support a staged model of human iPSC-cardiomyocyte maturation-associated transcriptional remodeling in which a reduction in cell-cycle-associated transcription is detectable before the subsequent decline in cardiomyocyte cell-cycle activity, thereby identifying distinct temporal patterns of cell-cycle and maturation-associated changes during prolonged hiPSC-CM culture.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Cardiovascular Research, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA",
    "The Heart Center, Nationwide Children’s Hospital, Columbus, OH 43205, USA",
    "Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH 43210, USA",
    "Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA",
    "Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA",
    "Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Shiqiao Ye",
      "orcid": "0000-0003-1529-7102"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rabina Shrestha"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yang Yu",
      "orcid": "0000-0001-6885-019X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Matthew Alonzo"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Cankun Wang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Qin Ma",
      "orcid": "0000-0002-3264-8392"
    },
    {
      "affs": [
        0,
        1,
        4,
        5
      ],
      "name": "Ming-Tao Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9c9gw0701xbn3.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15211936",
  "fulltext_url": null,
  "id": "9c9gw0701xbn3",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/21/1936",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Pluripotent Stem Cells Research"
    ]
  ],
  "openalex": "W7223667373",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/9c9gw0701xbn3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15211936",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/21/1936"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Pluripotent Stem Cells Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Live-Cell Monitoring and Transcriptomic Profiling Identify Distinct Temporal Patterns of Cell-Cycle Activity and Maturation in Human iPSC-Derived Cardiomyocytes",
  "title_text": "Live-Cell Monitoring and Transcriptomic Profiling Identify Distinct Temporal Patterns of Cell-Cycle Activity and Maturation in Human iPSC-Derived Cardiomyocytes",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:02Z",
  "url": "https://research.draconitic.com/paper/9c9gw0701xbn3",
  "venue": "Cells",
  "versions": []
}