{
  "abstract": "Genome maintenance is usually treated as cell-intrinsic, yet brain cells age within multicellular neighborhoods. Whether a cell's DNA damage response (DDR) state is systematically embedded in native tissue architecture is unknown. We used MERFISH to map curated repair programs across 604,252 cells in matched sections from 2-3 and 22-month-old mice. Regional DDR expression and coordination formed an age-dependent mosaic, accompanied by immune and oligodendroglial shifts. Independent metacell and distance-resolved analyses identified a consistent anchor-dependent organization. Low-DDR neurons occupied immune- and OPC-oligodendroglial-rich niches. In contrast, DDR-high vascular anchors were associated with vascular-cell enrichment and, in cortex and cerebral nuclei, OPC-oligodendroglial enrichment, whereas immune cells were enriched around DDR-low vascular anchors. Thus, genome-maintenance state was associated with distinct anchor-cell-specific spatial context depending on anchor-cell identity and its DDR transcriptional state. These opposing neuronal and vascular patterns define anchor-dependent genome-maintenance niches as a spatial feature of brain aging, with implications for regional vulnerability.",
  "abstract_shown": true,
  "affiliations": [
    "Penn State University College of Medicine, Neuroscience and Experimental Therapeutics Department, Hershey, PA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "A. Koshboresh"
    },
    {
      "name": "V. L. Roy"
    },
    {
      "name": "M. Abdelmageed"
    },
    {
      "name": "S. B. Manjila"
    },
    {
      "name": "D. Parmaksiz"
    },
    {
      "name": "Y. Kim"
    },
    {
      "name": "J. Gillis"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Paul"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ftexjg98dvmx.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.07.749801",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749801v1.full",
  "id": "5ftexjg98dvmx",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749801v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7212119329",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749801v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5ftexjg98dvmx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:56Z",
      "native_id": "10.64898/2026.09.07.749801",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749801v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Neuronal and vascular genome-maintenance states organize opposing multicellular architectures in the aging brain",
  "title_text": "Neuronal and vascular genome-maintenance states organize opposing multicellular architectures in the aging brain",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:53Z",
  "url": "https://research.draconitic.com/paper/5ftexjg98dvmx",
  "venue": "bioRxiv",
  "versions": []
}