A Spatial Multiomics Atlas and Resource for Immune-Fibrotic Niches in Chronic Kidney Allograft Dysfunction
9 affiliations
- 1Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230002, China .
- 2Department 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 .
- 3The Second Clinical Medical College, Nanjing Medical University, Nanjing 211166, China .
- 4Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China .
- 5Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210036, China .
- 6RagOmics, RageneBio Inc., Verona, New Jersey 07044, USA .
- 7Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China .
- 8Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China .
- 9Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 510120, China .
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.
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BibTeX
@article{gao2026spatial,
title = {{A Spatial Multiomics Atlas and Resource for Immune-Fibrotic Niches in Chronic Kidney Allograft Dysfunction}},
author = {Qiongqiong Gao and Zongpan Ke and Wenhao Xu and Ming Zheng and Bo Wang and Runmin Ding and Jiawen Liu and Zhou Hang and Ze Yu and Ke Ni and Huidong Su and Mulong Du and Mingyang Jiang and Dingwei Ye and Ruoyun Tan and Min Gu and Zijie Wang and Zeping Gui},
journal = {Cyborg and Bionic Systems},
year = {2026},
month = nov,
doi = {10.34133/cbsystems.0720},
url = {https://doi.org/10.34133/cbsystems.0720},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Spatial Multiomics Atlas and Resource for Immune-Fibrotic Niches in Chronic Kidney Allograft Dysfunction
AU - Qiongqiong Gao
AU - Zongpan Ke
AU - Wenhao Xu
AU - Ming Zheng
AU - Bo Wang
AU - Runmin Ding
AU - Jiawen Liu
AU - Zhou Hang
AU - Ze Yu
AU - Ke Ni
AU - Huidong Su
AU - Mulong Du
AU - Mingyang Jiang
AU - Dingwei Ye
AU - Ruoyun Tan
AU - Min Gu
AU - Zijie Wang
AU - Zeping Gui
PY - 2026
DA - 2026/11/05
JO - Cyborg and Bionic Systems
DO - 10.34133/cbsystems.0720
UR - https://doi.org/10.34133/cbsystems.0720
AB - 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.
SN - 2097-1087
SN - 2692-7632
ER -