{
  "abstract": "Thrombocytopenia-absent radius (TAR) syndrome is a rare disease characterized by thrombocytopenia that results from the defective differentiation of megakaryocyte (MK) precursors. It is caused by mutations in the exon junction complex member RBM8A; however, it is not understood how the deficiency in this gene leads to a defect in megakaryopoiesis. Using induced pluripotent stem cell lines derived from patients with TAR syndrome and isogenic lines with corrected expression of RBM8A, we compared the phenotypes of derivative hematopoietic progenitor cells (HPCs) and MK. Although the generation of HPCs was similar between lines, the proliferation of TAR MK was significantly reduced. This was accompanied by precocious maturation, differential expression of platelet signaling pathways, and enhanced apoptosis. Despite enhanced size and markers of maturation of TAR MK, TAR and corrected lines had similar platelet-forming capacity both in vitro and in vivo. Genome-wide gene expression analysis revealed differential gene expression in apoptosis and cell cycle pathways. Splicing analysis showed differential splicing of pathways involved in mRNA splicing and platelet degranulation, demonstrating lineage-specific defects. We also identified several candidate targets that could contribute to the phenotypes observed in this model. Overall, our study shows that the thrombocytopenia in TAR syndrome results from the lack of proliferation and increased cell death of MK progenitors, leading to fewer mature MK and platelets.",
  "abstract_shown": true,
  "affiliations": [
    "Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA",
    "Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA",
    "Division of Hematology, Children’s Hospital of Philadelphia, Philadelphia, PA",
    "Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia, Philadelphia, PA",
    "Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom",
    "Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium",
    "Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine and Children’s Hospital of Philadelphia, Philadelphia, PA",
    "Center for Computational and Genomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Catriana C. Nations"
    },
    {
      "affs": [
        1
      ],
      "name": "Jenea I. Adams"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicole Debruyne"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiuli Sim"
    },
    {
      "affs": [
        2
      ],
      "name": "Hyun Sook Ahn"
    },
    {
      "affs": [
        3
      ],
      "name": "C. J. Willett"
    },
    {
      "affs": [
        4
      ],
      "name": "James Warland"
    },
    {
      "affs": [
        4
      ],
      "name": "Cedric Ghevaert"
    },
    {
      "affs": [
        5
      ],
      "name": "Kathleen Freson"
    },
    {
      "affs": [
        3
      ],
      "name": "Giulia Pavani"
    },
    {
      "affs": [
        3
      ],
      "name": "Deborah L. French"
    },
    {
      "affs": [
        6
      ],
      "name": "Mortimer Poncz"
    },
    {
      "affs": [
        7
      ],
      "name": "Yi Xing"
    },
    {
      "affs": [
        3
      ],
      "name": "Lan Lin"
    },
    {
      "affs": [
        3
      ],
      "name": "Paul J. Gadue"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/06knv933nts7r.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bvth.2026.100201",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717861/?tool=EBI",
  "id": "06knv933nts7r",
  "issns": [
    "2950-3272"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13717861",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Disorders of Platelet Number and Function: Basic and Translational"
    ],
    [
      "openalex",
      "2720|Platelet Disorders and Treatments"
    ]
  ],
  "openalex": "W7202372778",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717861/pdf/?tool=EBI",
  "pmcid": "PMC13717861",
  "pmid": "42959987",
  "published": "2026-08-13",
  "publisher": "The American Society of Hematology",
  "ris": "https://research.draconitic.com/paper/06knv933nts7r.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:39Z",
      "native_id": "PMC:PMC13717861",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13717861"
    },
    {
      "first_seen": "2026-11-01T00:20:52Z",
      "native_id": "MED:42959987",
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      "url": "https://europepmc.org/article/MED/42959987"
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    {
      "first_seen": "2026-11-02T12:22:05Z",
      "native_id": "PMC13717861",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.bvth.2026.100201"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Platelet Disorders and Treatments",
      "subfield": "general"
    }
  ],
  "title": "An iPSC model of thrombocytopenia-absent radius syndrome links aberrant splicing to impaired megakaryopoiesis",
  "title_text": "An iPSC model of thrombocytopenia-absent radius syndrome links aberrant splicing to impaired megakaryopoiesis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:05Z",
  "url": "https://research.draconitic.com/paper/06knv933nts7r",
  "venue": "Blood vessels, thrombosis & hemostasis",
  "versions": []
}