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Updated: Aug 16, 2026
Supervised Machine Learning for Semi-Quantification of Extracellular DNA in Glomerulonephritis
Published on: June 18, 2020
Spatial transcriptomics reveals injury-responsive compartments and coordinated immune-fibrotic signaling in
Yucheng Tang1, Chunhua Zhu2, Shuang Chen1,2,3
1Institute for Big Data and Artificial Intelligence in Medicine, School of Science, China Pharmaceutical University, Nanjing, Jiangsu, China.
Objectives:
ANCA-associated vasculitis (AAV) presents with rapidly progressive glomerulonephritis, yet the tissue-level molecular landscape in pediatric AAV remains poorly understood. We aimed to characterize spatially resolved renal disease programs across different histopathological stages of pediatric AAV and compared with adult AAV.
Methods:
We applied spatial transcriptomics to renal biopsies from pediatric patients with AAV representing distinct histological classes defined by the Berden classification (4 control, 2 focal, and 3 non-focal cases), generating an in situ map of localized disease programs. Gene co-expression network and differential expression analyses were used to identify compartment-specific transcriptional programs and cell type markers, which were correlated with pathological indicators. Functional pathway and ligand-receptor interaction analyses were conducted to characterize lesion-associated signaling. Independent adult AAV spatial transcriptomic cohorts and immunofluorescence were used for validation.
Results:
Four disease-associated compartments-immune/interstitial fibroblasts (IM/Fib), glomeruli, myofibroblasts, and vascular compartments-showed distinct compartment-specific signatures that correlated with patient-level histopathology. We further identified coordinated immune-fibrotic signaling associated with different histopathological classes. Integrative analysis with an independent adult AAV spatial transcriptomic cohort revealed conserved core injury programs in glomerular and vascular compartments across age groups, layered with distinct age-dependent immunometabolic and stress-response signatures. Within IM/Fib, the CXCR4-CD74 receptor complex co-localized with IgM+ cells, and lumican (LUM) co-localized with collagen I/III; both were validated by immunofluorescence and associated with fibrotic injury. These findings were further corroborated using a larger dataset (n=38) of adult AAV patients.
Discussion:
These tissue-anchored signatures represent potential disease-associated molecular features with possible diagnostic relevance, and highlight the value of this foundational spatial transcriptomics map for generating testable hypotheses to be further evaluated in larger, stratified, treatment-annotated cohorts.
