{
  "abstract": "Human induced pluripotent stem cells (hiPSCs) are widely used for disease modelling and regenerative medicine, yet their utility depends on maintaining molecular integrity during long-term culture. BCOR (BCL6 Co-Repressor) mutations are among the most recurrent culture-acquired alterations in hiPSCs, but their functional consequences remain poorly understood. Here, we show that hiPSC BCOR mutations are predominantly truncating indels enriched in exon 7, defining a mutational landscape distinct from that observed in cancer. Multi-omics profiling reveals that BCOR loss drives widespread chromatin, transcriptomic and proteomic remodelling, with coordinated activation of developmental, pluripotency-associated and mitochondrial metabolism programmes. To facilitate routine surveillance, we develop a cost-effective TaqMan qPCR assay that accurately identifies BCOR-mutant hiPSCs across independent cell lines. Finally, we demonstrate that correction of BCOR mutation by CRISPR-Cas9 only partially restores the wildtype molecular state, highlighting the importance of early detection and monitoring of adaptive mutations in hiPSC cultures.",
  "abstract_shown": true,
  "affiliations": [
    "University of Cambridge"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "C. Badja"
    },
    {
      "name": "S. Boushaki"
    },
    {
      "name": "Y. Kumar"
    },
    {
      "name": "T. I. Roumeliotis"
    },
    {
      "name": "A. J. Curle"
    },
    {
      "name": "A. E. Guiloff"
    },
    {
      "name": "A. Degasperi"
    },
    {
      "name": "S. Momen"
    },
    {
      "name": "F. Robert"
    },
    {
      "name": "Y. Memari"
    },
    {
      "name": "S. Shooter"
    },
    {
      "name": "Z. Kozik"
    },
    {
      "name": "S. J. Zhao"
    },
    {
      "name": "P. J. Toong"
    },
    {
      "name": "I. Baker"
    },
    {
      "name": "B. Hendrich"
    },
    {
      "name": "R. A. Barker"
    },
    {
      "name": "J. Choudhary"
    },
    {
      "name": "G. C. C. Koh"
    },
    {
      "name": "S. Nik-Zainal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f29mv5ngf9yg2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.04.739550",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.739550v1.full",
  "id": "f29mv5ngf9yg2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.739550v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1312|Pluripotent Stem Cells Research"
    ]
  ],
  "openalex": "W7211966829",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.739550v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f29mv5ngf9yg2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:07Z",
      "native_id": "10.64898/2026.09.04.739550",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.04.739550v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "BCOR mutations establish a persistent culture-adaptive state in human induced pluripotent stem cells",
  "title_text": "BCOR mutations establish a persistent culture-adaptive state in human induced pluripotent stem cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:07Z",
  "url": "https://research.draconitic.com/paper/f29mv5ngf9yg2",
  "venue": "bioRxiv",
  "versions": []
}