Kidney Week

Abstract: TH-PO537

Kidney Tissue Single-Nucleus Multiomics Analysis of ANCA-Associated Glomerulonephritis Reveals Key Transcriptional Regulation Networks

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Zhang, Shuo, Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Shuo Zhang, PhD

• Xu, Lubin, Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Lubin Xu, MD

• Huang, Zheng, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Zheng Huang

• Yin, Saifu, Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu, China

Saifu Yin, PhD

• Li, Yun, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Yun Li

• Chen, Yanjie, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Yanjie Chen

• Meng, Xini, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Xini Meng

• Wang, Ying, Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Ying Wang

• Li, Jiaying, Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Jiaying Li

• Wen, Yubing, Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Yubing Wen, MD

• Zheng, Xixi, Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Xixi Zheng, MD

• Song, Turun, Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu, China

Turun Song, MD, PhD

• Lin, Tao, Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu, China

Tao Lin, MD, PhD

• Jiang, Lan, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Lan Jiang

• Chen, Limeng, Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Limeng Chen, MD, PhD

Background

We aimed to use single-cell nuclear RNA and chromatin accessibility (ATAC) sequencing on renal biopsy specimens from ANCA-associated glomerulonephritis (AAGN) patients to identify crucial pathways for further mechanistic studies

Methods

We studied five AAGN patients, ten healthy donors, and seven paraneoplastic renal tissues. SnRNA-Seq and snATAC-Seq performed with Universal Droplet-Based Single-Cell Combinational Indexed Sequencing technique. We used the Weighted Nearest Neighbor method for co-dimensional reduction of the multi-omics data, clustering, and cell type annotation via Seurat's Label Transfer method to identify differentially expressed genes and ATAC

Results

The patient group had an average age of 64±6 years, and the clinical manifestations were glomerulonephritis with acute kidney injury and the pathological manifestations of small-vessel vasculitis with crescent formation. Activated parietal epithelial cells (PECs) with high CD44 expression, up-regulated crescent-forming and development potential genes were enriched in AAGN kidneys. SCENIC+ identified E2F3 and BACH1 as core transcription factors (TF) in the regulatory network of activated PECs. Endothelial cell abnormalities were noted in peritubular capillaries (EC-PTCs) with up-regulated genes related to cell junction assembly and angiogenesis. SMAD1 and BACH1 were identified as key TFs of EC-PTC injury. AAGN patients had increased intercellular communication

Conclusion

Our study applied single-cell multi-omics sequencing to AAGN renal biopsies, revealing cell-specific transcriptomes and epigenetic profiles of PECs and EC-PTCs. This work provides insights into new mechanisms and potential therapeutic targets for AAGN

Funding

• Government Support – Non-U.S.