{
  "abstract": ". Transplantation of neural organoids into rodent hosts enables the in vivo study of aspects of human neurodevelopment and circuit function, alongside behavioural phenotyping of the host animals. However, spatial limitations and competition with host circuits constrain the integration of neural organoids, which is critical for studying disease. Here we establish a transplantation platform using a genetic strategy to effectively deplete glutamatergic neurons from mouse neocortex and hippocampus (apallial) and neonatally engraft the cortical cavity with human stem-cell-derived cortical organoids (hCO) to generate xenocortical mice. This leads to robust graft growth with hCOs occupying most of the cortical volume and generating a diversity of human cortical cell types, including layer 5 extratelencephalic projection neurons. Human cortical neurons integrate with the mouse nervous system, and in vivo cortical graft-wide calcium imaging and electrophysiological analyses revealed patterns of organized activity resembling developing circuits. Behavioural analyses of apallial and xenocortical mice revealed broadly preserved locomotion alongside selective differences in limb coordination and altered organization of spontaneous behaviour. Lastly, this platform enabled behavioural readouts in a model of injury to developing human cortical cells. We envision that xenocortication will be useful for obtaining circuit- and behaviour-level readouts using human neurons to study neurodevelopment, model disease and develop therapeutics.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA",
    "Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute & Bio-X, Stanford, CA, USA",
    "Department of Neurosurgery, Stanford University, Stanford, CA, USA",
    "Department of Bioengineering, Stanford University, Stanford, CA, USA",
    "BCBL-Basque Center on Cognition, Brain and Language, Donostia-San Sebastián, Spain",
    "IKERBASQUE-Basque Foundation for Science, Bilbao, Spain",
    "Department of Pathology, Stanford University, Stanford, CA, USA",
    "Department of Psychology, Stanford University, Stanford, CA, USA",
    "Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. spasca@stanford.edu",
    "Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute & Bio-X, Stanford, CA, USA. spasca@stanford.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Konstantin Kaganovsky",
      "orcid": "0000-0002-1577-109X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kevin W. Kelley",
      "orcid": "0000-0001-7262-6086"
    },
    {
      "affs": [
        2
      ],
      "name": "Tilo Gschwind",
      "orcid": "0000-0003-4261-218X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Paul M. Harary",
      "orcid": "0000-0002-4683-2115"
    },
    {
      "affs": [
        0
      ],
      "name": "John Kochalka",
      "orcid": "0000-0003-1044-6340"
    },
    {
      "affs": [
        3
      ],
      "name": "Alexander D. White",
      "orcid": "0000-0002-5387-310X"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Garikoitz Lerma‐Usabiaga",
      "orcid": "0000-0001-9800-4816"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaoyu Chen",
      "orcid": "0000-0003-4009-8156"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Omer Revah",
      "orcid": "0000-0002-4002-5689"
    },
    {
      "affs": [
        3,
        0
      ],
      "name": "Felicity Gore",
      "orcid": "0000-0003-4425-5534"
    },
    {
      "affs": [
        0
      ],
      "name": "Ayano Aoyama"
    },
    {
      "affs": [
        2
      ],
      "name": "Jennifer L. Shadrach",
      "orcid": "0009-0008-3064-118X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Se‐Jin Yoon",
      "orcid": "0000-0001-8412-5991"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alfredo M. Valencia",
      "orcid": "0000-0003-2432-9890"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Satoe Ogawa",
      "orcid": "0009-0001-0074-7185"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Noah Reis",
      "orcid": "0000-0002-7258-2463"
    },
    {
      "affs": [
        6
      ],
      "name": "Hannes S. Vogel",
      "orcid": "0000-0002-0960-3508"
    },
    {
      "affs": [
        7
      ],
      "name": "Brian Arie Wandell",
      "orcid": "0000-0002-2974-1836"
    },
    {
      "affs": [
        2
      ],
      "name": "Julia A. Kaltschmidt",
      "orcid": "0000-0002-2893-1793"
    },
    {
      "affs": [
        2
      ],
      "name": "Iván Soltész",
      "orcid": "0000-0003-1493-3744"
    },
    {
      "affs": [
        3,
        0
      ],
      "name": "Karl A. Deisseroth",
      "orcid": "0000-0001-9440-3967"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Sergiu P. Pașca",
      "orcid": "0000-0002-3216-3248"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f11k7yadb21wn.bib",
  "cited_by": 6,
  "doi": "10.1038/s41586-026-11032-2",
  "fulltext_url": null,
  "id": "f11k7yadb21wn",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-11032-2",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
    ]
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  "openalex": "W7213421814",
  "pdf_url": null,
  "pmcid": "PMC13645680",
  "pmid": "42749812",
  "published": "2026-09-16",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/f11k7yadb21wn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:53Z",
      "native_id": "W7213421814",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-11032-2"
    }
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Neurogenesis and neuroplasticity mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "Developmental xenocortication using human-derived organoids in mice",
  "title_text": "Developmental xenocortication using human-derived organoids in mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/f11k7yadb21wn",
  "venue": "Nature",
  "versions": []
}