{
  "abstract": "Chronic allograft dysfunction (CAD) is a major cause of late kidney-allograft failure, yet its spatially organized cellular and metabolic mechanisms remain poorly resolved because human biopsies are scarce and experimental models are imperfect. Here, we established a tacrolimus-modulated accelerated mouse model of CAD and constructed a cross-species multiomics atlas by integrating mouse single-cell RNA sequencing, flow cytometry, and multiplex imaging with human single-nucleus RNA sequencing, Visium HD spatial transcriptomics, and spatial metabolomics. Cross-species analysis revealed conserved immune, stromal, epithelial, and myeloid programs and delineated 2 anatomically distinct fibrotic niches. Cortical fibrosis was associated with endothelial/pericyte remodeling, altered cholesterol-biosynthesis transcriptional programs, and reduced regional cholesterol-related signals. Medullary fibrosis was enriched for proximal-tubule S3 [PT(S3)] cells with glycolysis-associated remodeling, increased regional lactate-related signals, and adjacent tissue-resident memory T-cell domains displaying an atypical exhaustion-like program. Glutamine/glutamate metabolism-associated programs accompanied inferred monocyte-to-macrophage state remodeling. In renal tubular epithelial cells, 2-deoxy-D-glucose partially attenuated transforming growth factor-β1-induced E-cadherin loss and α-smooth muscle actin induction, providing focused functional support for glycolysis-associated tubular remodeling. We additionally provide an exploratory kidney-transplant multiomics resource for data visualization, auxiliary summarization of platform-derived results, and gene/pathway querying. Together, this study provides a spatially resolved, cross-species framework for identifying candidate immune-metabolic mechanisms and prioritizing experimentally testable targets in CAD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230002, China .",
    "Department of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, Institute for Organ Injury and Repair, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210003, China .",
    "The Second Clinical Medical College, Nanjing Medical University, Nanjing 211166, China .",
    "Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China .",
    "Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210036, China .",
    "RagOmics, RageneBio Inc., Verona, New Jersey 07044, USA .",
    "Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China .",
    "Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China .",
    "Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 510120, China ."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qiongqiong Gao"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Zongpan Ke"
    },
    {
      "affs": [
        3
      ],
      "name": "Wenhao Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Ming Zheng"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Bo Wang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Runmin Ding"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiawen Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhou Hang"
    },
    {
      "affs": [
        5
      ],
      "name": "Ze Yu"
    },
    {
      "affs": [
        5
      ],
      "name": "Ke Ni",
      "orcid": "0000-0002-5437-9963"
    },
    {
      "affs": [
        6
      ],
      "name": "Huidong Su"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Mulong Du"
    },
    {
      "affs": [
        8
      ],
      "name": "Mingyang Jiang"
    },
    {
      "affs": [
        3
      ],
      "name": "Dingwei Ye"
    },
    {
      "affs": [
        4
      ],
      "name": "Ruoyun Tan"
    },
    {
      "affs": [
        1
      ],
      "name": "Min Gu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zijie Wang"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Zeping Gui",
      "orcid": "0000-0003-1537-8586"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8nc0ayq62qm6h.bib",
  "cited_by": 0,
  "doi": "10.34133/cbsystems.0720",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735209/",
  "id": "8nc0ayq62qm6h",
  "issns": [
    "2097-1087",
    "2692-7632"
  ],
  "landing_url": "https://doi.org/10.34133/cbsystems.0720",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2747|Renal Transplantation Outcomes and Treatments"
    ]
  ],
  "openalex": "W7214743742",
  "pdf_url": null,
  "pmcid": "PMC13735209",
  "pmid": "42990767",
  "published": "2026-11-05",
  "publisher": "AAAS Science Partner Journal Program",
  "ris": "https://research.draconitic.com/paper/8nc0ayq62qm6h.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:20:56Z",
      "native_id": "PMC13735209",
      "source": "pmc",
      "url": "https://doi.org/10.34133/cbsystems.0720"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2747|Renal Transplantation Outcomes and Treatments",
      "subfield": "surgery"
    }
  ],
  "title": "A Spatial Multiomics Atlas and Resource for Immune-Fibrotic Niches in Chronic Kidney Allograft Dysfunction",
  "title_text": "A Spatial Multiomics Atlas and Resource for Immune-Fibrotic Niches in Chronic Kidney Allograft Dysfunction",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:20:56Z",
  "url": "https://research.draconitic.com/paper/8nc0ayq62qm6h",
  "venue": "Cyborg and Bionic Systems",
  "versions": []
}