{
  "abstract": "BACKGROUND: Glioblastoma is the deadliest brain cancer, characterized by large cellular diversity. Both neurodevelopment-like and mesenchymal-like cell states have been described, with the latter being strongly implicated in malignancy and disease progression. However, the spatial organization of these mesenchymal-like cell states has not been systematically described outside the tumor bulk. METHODS: We performed deep single-cell RNA sequencing of rare glioblastoma cases where tissue could be sampled from tumor core to macroscopically normal cortex and 888-plex enhanced electric single-molecule fluorescence in situ hybridization (EEL-FISH) spatial transcriptomics on a large cohort of standard resections. We also established four glioblastoma organoid lines to test in vitro inducibility of mesenchymal-like cell states under hypoxia and blood plasma exposure. FINDINGS: We discovered that previously defined mesenchymal-like tumor cell states were shared across both malignant and non-malignant cell types and spatially confined to the tumor bulk. Peripheral regions were instead dominated by neurodevelopment-like tumor states and endogenous microglia. In patient-derived organoids and non-malignant astrocytes, the mesenchymal transcriptional state could be reversibly induced in vitro by hypoxia and human plasma, indicative of a wound response. Multiplex single-molecule spatial transcriptomics revealed that the activation of mesenchymal-like states was associated with hypoxia and organized by distance to perivascular niches. CONCLUSIONS: Our findings clarify the cellular landscape and biology of glioblastoma, wherein the mesenchymal state arises at least partly as a reactive tissue state shared by all cells in the tumor bulk. FUNDING: This work was supported by Region Stockholm, Erling-Persson Family Foundation (Atlas of Childhood Disease), Hjärnfonden (FO2023-0309), Swedish Research Council (2022-01248), and Torsten Söderberg Foundation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden",
    "Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, 17164 Stockholm, Sweden",
    "Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 17164 Stockholm, Sweden",
    "Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden; Center for Brain & Disease Research, VIB, 3000 Leuven, Belgium; Center for AI & Computational Biology, VIB, 3000 Leuven, Belgium; Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium",
    "Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 17164 Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institute, 17177 Stockholm, Sweden",
    "Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden; Department of Translational Neuroscience, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands",
    "Department of Clinical Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, 17164 Stockholm, Sweden",
    "Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden. Electronic address: sten.linnarsson@ki.se"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alejandro Mossi Albiach",
      "orcid": "0000-0001-7009-4901"
    },
    {
      "affs": [
        0
      ],
      "name": "Jokubas Janusauskas",
      "orcid": "0000-0002-9128-4218"
    },
    {
      "affs": [
        1
      ],
      "name": "Jesper Kjaer Jacobsen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ivana Kapustová",
      "orcid": "0009-0006-9599-757X"
    },
    {
      "affs": [
        0
      ],
      "name": "Razieh Karamzadeh",
      "orcid": "0000-0002-6148-3398"
    },
    {
      "affs": [
        2
      ],
      "name": "Egle Kvedaraite",
      "orcid": "0000-0001-5308-092X"
    },
    {
      "affs": [
        0
      ],
      "name": "Lijuan Hu",
      "orcid": "0000-0002-6889-1650"
    },
    {
      "affs": [
        0
      ],
      "name": "Marina C. M. Franck",
      "orcid": "0000-0002-2174-6392"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Ramal García"
    },
    {
      "affs": [
        0
      ],
      "name": "David Fernández-García",
      "orcid": "0000-0002-0232-8478"
    },
    {
      "affs": [
        3
      ],
      "name": "Camiel C. A. Mannens",
      "orcid": "0000-0002-1318-2603"
    },
    {
      "affs": [
        0
      ],
      "name": "Simone Codeluppi",
      "orcid": "0000-0002-7053-0520"
    },
    {
      "affs": [
        0
      ],
      "name": "Johannes B. Munting",
      "orcid": "0009-0007-9386-9037"
    },
    {
      "affs": [
        3
      ],
      "name": "Lars E. Borm",
      "orcid": "0000-0002-1764-6057"
    },
    {
      "affs": [
        4
      ],
      "name": "Alia Shamikh",
      "orcid": "0009-0003-2972-5355"
    },
    {
      "affs": [
        0
      ],
      "name": "Peter Lönnerberg",
      "orcid": "0009-0009-0965-2906"
    },
    {
      "affs": [
        5
      ],
      "name": "Kimberly Siletti",
      "orcid": "0000-0001-7620-8973"
    },
    {
      "affs": [
        6
      ],
      "name": "Oscar Persson",
      "orcid": "0000-0001-5906-7443"
    },
    {
      "affs": [
        7
      ],
      "name": "Sten Linnarsson",
      "orcid": "0000-0002-3491-3444"
    }
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  "bibtex": "https://research.draconitic.com/paper/0vgded195r810.bib",
  "cited_by": 26,
  "doi": "10.1016/j.medj.2026.101228",
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  "id": "0vgded195r810",
  "issns": [
    "2666-6340",
    "2666-6359"
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  "landing_url": "https://doi.org/10.1016/j.medj.2026.101228",
  "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": [
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  "pmid": "42492522",
  "published": "2026-07-23",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/0vgded195r810.ris",
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  "title": "Tissue-reactive zonation of mesenchymal-like phenotypes in human glioblastoma",
  "title_text": "Tissue-reactive zonation of mesenchymal-like phenotypes in human glioblastoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T13:21:05Z",
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