{
  "abstract": "Colorectal cancer develops through a normal-adenoma-carcinoma sequence, yet only 5-10% of adenomas progress to malignancy, and the cellular programs governing that sequence remain poorly defined. Here we generate a spatial multi-omics atlas of human colon adenomas, combining Visium CytAssist and protein co-detection across 24 nonadvanced and advanced tubular adenomas with single-cell resolution Xenium Prime 5K profiling of 101 patient-matched normal, adenoma, and carcinoma cores from 16 patients. Integrating whole-transcriptome and 31-plex protein data identifies nine spatial clusters and two dysplastic epithelial populations that co-express stemness, proliferation, and senescence programs. These programs occupy a shared, spatially confined epithelial niche that expands from adenoma to carcinoma. Spatial analysis revealed GDF15, a senescence-associated secretory factor, mediated the coupling between senescence and stemness in advanced adenomas, and that GDF15-high epithelium locally excludes CD8+ T cells in adenoma and, more broadly, in carcinoma. These findings position senescence as a spatially instructive rather than merely tumor-suppressive program during colorectal carcinogenesis and suggest GDF15 might be a potential candidate target for cancer prevention and interception in the colon.",
  "abstract_shown": true,
  "affiliations": [
    "Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. Yu"
    },
    {
      "name": "Y. Xie"
    },
    {
      "name": "L. Allen"
    },
    {
      "name": "K. Carter"
    },
    {
      "name": "E. Donato"
    },
    {
      "name": "L. Cheng"
    },
    {
      "name": "C. Kendziorski"
    },
    {
      "name": "K. A. Matkowskyj"
    },
    {
      "name": "A. M. De Marzo"
    },
    {
      "name": "J. Hicks"
    },
    {
      "name": "D. Reddi"
    },
    {
      "name": "E. W. Newell"
    },
    {
      "name": "W. Sun"
    },
    {
      "name": "W. M. Grady"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0gevtjqk7zr6z.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.06.743310",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.06.743310v2.full",
  "id": "0gevtjqk7zr6z",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.06.743310v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7201878165",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.06.743310v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0gevtjqk7zr6z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:23Z",
      "native_id": "10.64898/2026.08.06.743310",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.06.743310v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Spatial multi-omics and single-cell transcriptomics uncover senescence-associated cellular programs during colon adenoma to cancer progression",
  "title_text": "Spatial multi-omics and single-cell transcriptomics uncover senescence-associated cellular programs during colon adenoma to cancer progression",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:23Z",
  "url": "https://research.draconitic.com/paper/0gevtjqk7zr6z",
  "venue": "bioRxiv",
  "versions": []
}