{
  "abstract": ". However, how these malignant states arise and whether they follow defined cellular trajectories across tumours is poorly understood. Here we generated a deep single-cell and spatial multi-omic atlas of human glioblastoma that pairs transcriptomic, epigenomic and genomic profiling of 12 tumours across many regions. We identify that glioblastoma heterogeneity is driven by spatially patterned transitions of cancer cells from developmental-like states towards those defined by a glial injury response and hypoxia. This cellular trajectory regionalizes tumours into distinct tissue microenvironments and manifests in a molecularly conserved manner across tumours as well as genetically distinct tumour subclones. Consistently, using a new deep-learning framework to map cancer cell states jointly with clones in situ, we show that tumour subclones are finely spatially intermixed through glioblastoma tissue microenvironments. We validate this cellular trajectory by using somatic mutation-based hierarchies in vivo and an experimental patient-derived organoid model ex vivo. Finally, we show that this cancer cell trajectory is intimately linked to myeloid heterogeneity and unfolds across regionalized myeloid signalling environments. Our findings define a stereotyped trajectory of cancer cells in glioblastoma and unify glioblastoma tumour heterogeneity into a tractable cellular and tissue framework.",
  "abstract_shown": true,
  "affiliations": [
    "Wellcome Sanger Institute, Cambridge, UK",
    "Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany",
    "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany",
    "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK",
    "Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge, UK",
    "Department of Neurosurgery, Cedars-Sinai Guerin Children's, Los Angeles, CA, USA",
    "Department of Paediatrics, University of Cambridge, Cambridge, UK",
    "Department of Pediatrics, Cedars-Sinai Guerin Children's, Los Angeles, CA, USA",
    "The Francis Crick Institute, London, UK",
    "Faculty of Medicine, Heidelberg University, Heidelberg, Germany",
    "Institute for Computational Biomedicine, Heidelberg University Hospital, Heidelberg, Germany",
    "International School of Medicine, Istanbul Medipol University, Istanbul, Turkey",
    "Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK",
    "Cell Fate Engineering and Disease Modeling Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany",
    "Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany",
    "HITBR Hector Institute for Translational Brain Research gGmbH, Heidelberg, Germany",
    "Division of AI in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany",
    "Faculty of Biosciences, Heidelberg University, Heidelberg, Germany",
    "Faculty of Mathematics and Computer Science, Heidelberg University, Heidelberg, Germany",
    "European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK",
    "Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK. richard.mair@cruk.cam.ac.uk",
    "Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge, UK. richard.mair@cruk.cam.ac.uk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 63,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Grant de Jong",
      "orcid": "0000-0002-5614-9651"
    },
    {
      "affs": [
        0
      ],
      "name": "Fani Memi",
      "orcid": "0000-0002-3685-1988"
    },
    {
      "affs": [
        0
      ],
      "name": "Tannia Gracia",
      "orcid": "0000-0002-8237-1870"
    },
    {
      "affs": [
        1,
        2,
        0
      ],
      "name": "Olga Lazareva",
      "orcid": "0000-0001-9546-7807"
    },
    {
      "affs": [
        0
      ],
      "name": "Oliver Gould",
      "orcid": "0009-0009-9374-4511"
    },
    {
      "affs": [
        3,
        4,
        0
      ],
      "name": "Georgios Solomou",
      "orcid": "0000-0002-9795-0517"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexander Aivazidis"
    },
    {
      "affs": [
        0
      ],
      "name": "Manàs Dave",
      "orcid": "0000-0002-1676-801X"
    },
    {
      "affs": [
        5,
        6,
        7,
        0
      ],
      "name": "Qianqian Zhang"
    },
    {
      "affs": [
        8
      ],
      "name": "Melanie Jensen"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Ahmet Süreyya Rifaioğlu",
      "orcid": "0000-0001-6717-4767"
    },
    {
      "affs": [
        8
      ],
      "name": "João Diogo Barros-Silva",
      "orcid": "0000-0002-6648-0217"
    },
    {
      "affs": [
        0
      ],
      "name": "Sabine Eckert",
      "orcid": "0000-0001-8530-1029"
    },
    {
      "affs": [
        0
      ],
      "name": "Di Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Yvette Wood"
    },
    {
      "affs": [
        0
      ],
      "name": "Elizabeth J. Tuck",
      "orcid": "0000-0002-1837-7549"
    },
    {
      "affs": [
        11,
        0
      ],
      "name": "Sezgin Er",
      "orcid": "0000-0001-7266-9844"
    },
    {
      "affs": [
        0
      ],
      "name": "Koen Rademaker",
      "orcid": "0000-0003-3059-5183"
    },
    {
      "affs": [
        0
      ],
      "name": "Robert Petryszak",
      "orcid": "0000-0001-6333-2182"
    },
    {
      "affs": [
        0
      ],
      "name": "Henry Marshall"
    },
    {
      "affs": [
        0
      ],
      "name": "Kenny Roberts",
      "orcid": "0000-0001-6155-0821"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrew L. Trinh",
      "orcid": "0000-0001-6547-5494"
    },
    {
      "affs": [
        0
      ],
      "name": "Shreya Rai"
    },
    {
      "affs": [
        12,
        4
      ],
      "name": "Tyler Shaw",
      "orcid": "0000-0001-6041-2494"
    },
    {
      "affs": [
        0
      ],
      "name": "Ágnes Oszlánczi",
      "orcid": "0000-0001-6148-6591"
    },
    {
      "affs": [
        0
      ],
      "name": "Hayden Powell"
    },
    {
      "affs": [
        0
      ],
      "name": "Pavel Mazin",
      "orcid": "0000-0001-9268-3352"
    },
    {
      "affs": [
        0
      ],
      "name": "Stanislaw Makarchuk",
      "orcid": "0000-0001-5484-7141"
    },
    {
      "affs": [
        0
      ],
      "name": "Yinshui Chang",
      "orcid": "0000-0003-3538-6663"
    },
    {
      "affs": [
        0
      ],
      "name": "Katarzyna Kania",
      "orcid": "0000-0001-8206-1349"
    },
    {
      "affs": [
        0
      ],
      "name": "Liying Jin",
      "orcid": "0009-0001-4442-7298"
    },
    {
      "affs": [
        0
      ],
      "name": "Catherine L. Tudor",
      "orcid": "0000-0003-2093-9683"
    },
    {
      "affs": [
        0
      ],
      "name": "Hon Man Chan"
    },
    {
      "affs": [
        0
      ],
      "name": "Harriet F. Johnson",
      "orcid": "0000-0003-0075-5297"
    },
    {
      "affs": [
        0
      ],
      "name": "Benjamin Rumney"
    },
    {
      "affs": [
        0
      ],
      "name": "Holly E. Anderson",
      "orcid": "0009-0006-9721-0048"
    },
    {
      "affs": [
        0
      ],
      "name": "Jasmine Ellis",
      "orcid": "0009-0008-0857-7003"
    },
    {
      "affs": [
        0
      ],
      "name": "Vanessa Brito Pereira"
    },
    {
      "affs": [
        0
      ],
      "name": "Zoi Katsirea",
      "orcid": "0009-0009-3815-4922"
    },
    {
      "affs": [
        0
      ],
      "name": "Irfan Mamun"
    },
    {
      "affs": [
        0
      ],
      "name": "Ilaria Mulas",
      "orcid": "0000-0003-2556-9685"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Annelies Quaegebeur",
      "orcid": "0000-0001-5357-9341"
    },
    {
      "affs": [
        12
      ],
      "name": "Mayen Briggs"
    },
    {
      "affs": [
        0
      ],
      "name": "Jessica Cox",
      "orcid": "0000-0002-1109-1679"
    },
    {
      "affs": [
        0
      ],
      "name": "Jimmy Tsz Hang Lee",
      "orcid": "0000-0003-1208-8356"
    },
    {
      "affs": [
        13,
        14,
        15
      ],
      "name": "Laura Rueda-Gensini",
      "orcid": "0000-0003-0138-7393"
    },
    {
      "affs": [
        13,
        14,
        1,
        2,
        15
      ],
      "name": "Manu Saraswat",
      "orcid": "0000-0002-1472-8049"
    },
    {
      "affs": [
        16,
        17
      ],
      "name": "Zaira Seferbevoka"
    },
    {
      "affs": [
        6
      ],
      "name": "Adam Young"
    },
    {
      "affs": [
        0
      ],
      "name": "Minal Patel"
    },
    {
      "affs": [
        0
      ],
      "name": "Tarryn Porter",
      "orcid": "0000-0002-6063-0659"
    },
    {
      "affs": [
        16,
        18
      ],
      "name": "Moritz Gerstung"
    },
    {
      "affs": [
        0
      ],
      "name": "Martin Prete",
      "orcid": "0000-0002-5946-821X"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Prigmore",
      "orcid": "0000-0001-8870-0316"
    },
    {
      "affs": [
        13,
        14,
        15
      ],
      "name": "Moritz Mall",
      "orcid": "0000-0002-1278-2594"
    },
    {
      "affs": [
        3,
        4,
        6
      ],
      "name": "Harry Bulstrode"
    },
    {
      "affs": [
        19,
        9,
        10
      ],
      "name": "Julio Sáez-Rodríguez",
      "orcid": "0000-0002-8552-8976"
    },
    {
      "affs": [
        8
      ],
      "name": "James Briscoe",
      "orcid": "0000-0002-1020-5240"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "David H. Rowitch",
      "orcid": "0000-0002-0079-0060"
    },
    {
      "affs": [
        20,
        21
      ],
      "name": "Richard James Mair",
      "orcid": "0000-0001-8235-5689"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bnc7zgyj4p87w.bib",
  "cited_by": 9,
  "doi": "10.1038/s41586-026-11234-8",
  "fulltext_url": null,
  "id": "bnc7zgyj4p87w",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-11234-8",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W4410357547",
  "pdf_url": "https://www.nature.com/articles/s41586-026-11234-8.pdf",
  "pmcid": null,
  "pmid": "42983086",
  "published": "2026-11-04",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/bnc7zgyj4p87w.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T13:20:49Z",
      "native_id": "W4410357547",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-11234-8"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A spatiotemporal cancer cell trajectory underlies glioblastoma heterogeneity",
  "title_text": "A spatiotemporal cancer cell trajectory underlies glioblastoma heterogeneity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T13:20:49Z",
  "url": "https://research.draconitic.com/paper/bnc7zgyj4p87w",
  "venue": "Nature",
  "versions": []
}