{
  "abstract": "Understanding how the first cell lineages in human development are specified and maintained has fundamental importance and clinical implications for regenerative medicine, infertility and pregnancy loss. Although mouse models have provided valuable insights into transcription factors regulating early development, translating these findings to human embryos has been limited by ethical, technical and biological constraints. Functional studies of transcription factors in human embryos have been hindered by nuclease-based genome editing approaches that induce genotoxicity 1–3 . Here, to overcome this, we applied ABE8e adenine base editing 4,5 to precisely target an exon splice donor site, resulting in a splicing defect and functional knockout of the developmental regulator NANOG in human embryos. This approach did not trigger genotoxicity and showed limited off-target editing. Loss of NANOG disrupts pluripotent epiblast specification and instead cells differentiate towards a primitive endoderm (yolk sac) or trophectoderm (placental) transcriptional programme. Retention of primitive endoderm differentiation in NANOG -edited human embryos reveals a functional compensation that is distinct from mouse, underscoring the importance of directly investigating human development. Our findings demonstrate an essential role for NANOG in human pluripotency and epiblast specification and highlight the utility of base editing for functional interrogation of human development.",
  "abstract_shown": true,
  "affiliations": [
    "Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, UK",
    "Loke Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK",
    "MRC Laboratory of Molecular Biology, Cambridge, UK",
    "Assisted Reproduction and Gynaecology Centre, London, UK",
    "Create Fertility, London, UK",
    "Centre for Reproductive and Genetic Health, London, UK",
    "Newcastle Fertility Centre, Newcastle upon Tyne Hospitals NHS Trust, Biosciences Institute, Newcastle University Centre for Life, Newcastle upon Tyne, UK",
    "Bourn Hall Clinic, Bourn, UK",
    "Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA",
    "Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA",
    "Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA",
    "Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Boston, MA, USA",
    "Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA",
    "Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia",
    "Loke Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. kh767@cam.ac.uk",
    "Sidney Sussex College, Cambridge, UK. kh767@cam.ac.uk",
    "Epigenetics Programme, Babraham Institute, Cambridge, UK. kkn21@cam.ac.uk",
    "Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, UK. kkn21@cam.ac.uk",
    "Loke Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. kkn21@cam.ac.uk",
    "Wellcome Trust - Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. kkn21@cam.ac.uk"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Oliver J. Bower"
    },
    {
      "affs": [
        1
      ],
      "name": "Ana Elisa Ribeiro Orsi",
      "orcid": "0000-0002-4939-1423"
    },
    {
      "affs": [
        1
      ],
      "name": "Riley McMahon",
      "orcid": "0000-0002-4358-569X"
    },
    {
      "affs": [
        1
      ],
      "name": "Desislava P. Staneva",
      "orcid": "0000-0003-1330-2158"
    },
    {
      "affs": [
        1
      ],
      "name": "Josephine R. Blagrove",
      "orcid": "0000-0003-2765-3514"
    },
    {
      "affs": [
        2
      ],
      "name": "Kashish Singh",
      "orcid": "0000-0002-9891-8148"
    },
    {
      "affs": [
        1
      ],
      "name": "Claire S. Simon",
      "orcid": "0000-0001-9614-1403"
    },
    {
      "affs": [
        0
      ],
      "name": "Afshan McCarthy",
      "orcid": "0009-0005-5450-8496"
    },
    {
      "affs": [
        3
      ],
      "name": "Patricia Garcia",
      "orcid": "0009-0009-9499-9401"
    },
    {
      "affs": [
        3
      ],
      "name": "Valerie Shaikly"
    },
    {
      "affs": [
        3
      ],
      "name": "Mohamed Taranissi"
    },
    {
      "affs": [
        4
      ],
      "name": "Martin Wilding",
      "orcid": "0000-0003-1829-6850"
    },
    {
      "affs": [
        5
      ],
      "name": "Paul F. Serhal"
    },
    {
      "affs": [
        5
      ],
      "name": "Rabi A. Odia",
      "orcid": "0000-0001-6384-2764"
    },
    {
      "affs": [
        5
      ],
      "name": "Mina Vasilic"
    },
    {
      "affs": [
        6
      ],
      "name": "Meenakshi Choudhary"
    },
    {
      "affs": [
        7
      ],
      "name": "Athanasios Papathanasiou",
      "orcid": "0000-0002-5541-1769"
    },
    {
      "affs": [
        7
      ],
      "name": "Kay T. Elder",
      "orcid": "0000-0003-3510-8268"
    },
    {
      "affs": [
        7
      ],
      "name": "Phil Snell"
    },
    {
      "affs": [
        7
      ],
      "name": "Leila Christie"
    },
    {
      "affs": [
        8,
        9,
        10,
        11
      ],
      "name": "Mandana Arbab",
      "orcid": "0000-0001-9216-5096"
    },
    {
      "affs": [
        8,
        12,
        10
      ],
      "name": "David R. Liu",
      "orcid": "0000-0002-9943-7557"
    },
    {
      "affs": [
        13,
        6
      ],
      "name": "Mary Herbert",
      "orcid": "0000-0002-8488-2770"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "Katarina Harasimov",
      "orcid": "0000-0003-2703-4342"
    },
    {
      "affs": [
        16,
        17,
        18,
        19
      ],
      "name": "Kathy K. Niakan",
      "orcid": "0000-0003-1646-4734"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1f4vh9pc1p9hd.bib",
  "cited_by": 9,
  "doi": "10.1038/s41586-026-10792-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13716833/",
  "id": "1f4vh9pc1p9hd",
  "issns": [
    "0028-0836",
    "1476-4687"
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  "landing_url": "https://doi.org/10.1038/s41586-026-10792-1",
  "language": "en",
  "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,
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  "pdf_url": null,
  "pmcid": "PMC13716833",
  "pmid": "42350792",
  "published": "2026-06-25",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/1f4vh9pc1p9hd.ris",
  "sources": [
    {
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      "field": "biochemistry",
      "origin": "openalex:1312|Pluripotent Stem Cells Research",
      "subfield": "molecular-biology"
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  ],
  "title": "Base editing reveals an essential role for NANOG in human embryogenesis",
  "title_text": "Base editing reveals an essential role for NANOG in human embryogenesis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:43Z",
  "url": "https://research.draconitic.com/paper/1f4vh9pc1p9hd",
  "venue": "Nature",
  "versions": []
}