{
  "abstract": "Understanding early cardiac developmental abnormalities requires linking tissue phenotypes to the cellular populations produced during differentiation. We established a cardiac organoid platform derived from human induced pluripotent stem cells (hiPSCs) and combined phenotypic assays, time-course and day-9 single-cell transcriptomics, and cleavage under targets and tagmentation (CUT&Tag) to investigate developmental perturbations. Organoids contained multiple cell populations and exhibited stage-dependent cardiac transcriptional programs. Thalidomide exposure altered morphology and reduced TNNT2-positive tissue area, with lower calcium transient amplitude at 0.01 μg/mL. RNA sequencing at 10 μg/mL identified downregulation of heart and neural crest derivatives expressed 1 (HAND1), prompting a separate genetic investigation. Across three paired differentiation experiments using one characterized HAND1-knockout clone, reduced cardiomyocyte representation accompanied relative enrichment of mesodermal/mesenchymal-like cells. Selected cardiac-associated expression abnormalities persisted at day 15. Expression and chromatin occupancy analyses identified candidate regulatory associations, with locus-specific quantitative PCR supporting HAND1 occupancy at selected cardiac-associated regions. Independent genetic and functional validation is needed to test causal relationships. Together, these findings place HAND1 loss-associated tissue abnormalities in their cellular context and identify candidate occupied regions for investigating early cardiac differentiation in a human three-dimensional model.",
  "abstract_shown": true,
  "affiliations": [
    "School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China",
    "China State Institute of Pharmaceutical Industry Co., Ltd., Shanghai 201203, China",
    "Shanghai InnoStar Bio-Tech Co., Ltd., Shanghai 201203, China",
    "Innovation Center for AI and Drug Discovery, School of Pharmacy, East China Normal University, Shanghai 200062, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hao Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yunqian Zeng"
    },
    {
      "affs": [
        2
      ],
      "name": "Yiyang Teng"
    },
    {
      "affs": [
        2
      ],
      "name": "Qi Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Minbo Hou"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhikai Cheng"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Xuemei Zhang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Xijie Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e8k59x5f1snhq.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15211948",
  "fulltext_url": null,
  "id": "e8k59x5f1snhq",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/21/1948",
  "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": "W7223987484",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/e8k59x5f1snhq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15211948",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/21/1948"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Pluripotent Stem Cells Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Human Cardiac Organoids Reveal HAND1 Loss-Associated Alterations in Cell Composition During Early Cardiac Differentiation",
  "title_text": "Human Cardiac Organoids Reveal HAND1 Loss-Associated Alterations in Cell Composition During Early Cardiac Differentiation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:02Z",
  "url": "https://research.draconitic.com/paper/e8k59x5f1snhq",
  "venue": "Cells",
  "versions": []
}