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Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients

Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease of the kidney glomerulus. It may gradually progress to end-stage renal disease (ESRD) characterized by increased proteinuria, which leads to serious consequences. Although substantial advances have been made in the under...

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Autores principales: Xu, Jie, Shen, Chanjuan, Lin, Wei, Meng, Ting, Ooi, Joshua D., Eggenhuizen, Peter J., Tang, Rong, Xiao, Gong, Jin, Peng, Ding, Xiang, Tang, Yangshuo, Peng, Weisheng, Nie, Wannian, Ao, Xiang, Xiao, Xiangcheng, Zhong, Yong, Zhou, Qiaoling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202011/
https://www.ncbi.nlm.nih.gov/pubmed/34135910
http://dx.doi.org/10.3389/fimmu.2021.683330
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author Xu, Jie
Shen, Chanjuan
Lin, Wei
Meng, Ting
Ooi, Joshua D.
Eggenhuizen, Peter J.
Tang, Rong
Xiao, Gong
Jin, Peng
Ding, Xiang
Tang, Yangshuo
Peng, Weisheng
Nie, Wannian
Ao, Xiang
Xiao, Xiangcheng
Zhong, Yong
Zhou, Qiaoling
author_facet Xu, Jie
Shen, Chanjuan
Lin, Wei
Meng, Ting
Ooi, Joshua D.
Eggenhuizen, Peter J.
Tang, Rong
Xiao, Gong
Jin, Peng
Ding, Xiang
Tang, Yangshuo
Peng, Weisheng
Nie, Wannian
Ao, Xiang
Xiao, Xiangcheng
Zhong, Yong
Zhou, Qiaoling
author_sort Xu, Jie
collection PubMed
description Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease of the kidney glomerulus. It may gradually progress to end-stage renal disease (ESRD) characterized by increased proteinuria, which leads to serious consequences. Although substantial advances have been made in the understanding of the molecular bases of IMN in the last 10 years, certain questions remain largely unanswered. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from 6 patients with anti-PLA2R positive IMN and 2 healthy control subjects using single-cell RNA sequencing. We then identified distinct cell clusters through unsupervised clustering analysis of kidney specimens. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. Based on transcriptional expression patterns, we identified all previously described cell types in the kidney. The DEGs in most kidney parenchymal cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling, and MAPK signaling. Moreover, cell-cell crosstalk highlighted the extensive communication of mesangial cells, which infers great importance in IMN. IMN with massive proteinuria displayed elevated expression of genes participating in inflammatory signaling pathways that may be involved in the pathogenesis of the progression of IMN. Overall, we applied single-cell RNA sequencing to IMN to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis, and identify novel therapeutic targets of anti-PLA2R positive IMN.
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spelling pubmed-82020112021-06-15 Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients Xu, Jie Shen, Chanjuan Lin, Wei Meng, Ting Ooi, Joshua D. Eggenhuizen, Peter J. Tang, Rong Xiao, Gong Jin, Peng Ding, Xiang Tang, Yangshuo Peng, Weisheng Nie, Wannian Ao, Xiang Xiao, Xiangcheng Zhong, Yong Zhou, Qiaoling Front Immunol Immunology Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease of the kidney glomerulus. It may gradually progress to end-stage renal disease (ESRD) characterized by increased proteinuria, which leads to serious consequences. Although substantial advances have been made in the understanding of the molecular bases of IMN in the last 10 years, certain questions remain largely unanswered. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from 6 patients with anti-PLA2R positive IMN and 2 healthy control subjects using single-cell RNA sequencing. We then identified distinct cell clusters through unsupervised clustering analysis of kidney specimens. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. Based on transcriptional expression patterns, we identified all previously described cell types in the kidney. The DEGs in most kidney parenchymal cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling, and MAPK signaling. Moreover, cell-cell crosstalk highlighted the extensive communication of mesangial cells, which infers great importance in IMN. IMN with massive proteinuria displayed elevated expression of genes participating in inflammatory signaling pathways that may be involved in the pathogenesis of the progression of IMN. Overall, we applied single-cell RNA sequencing to IMN to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis, and identify novel therapeutic targets of anti-PLA2R positive IMN. Frontiers Media S.A. 2021-05-31 /pmc/articles/PMC8202011/ /pubmed/34135910 http://dx.doi.org/10.3389/fimmu.2021.683330 Text en Copyright © 2021 Xu, Shen, Lin, Meng, Ooi, Eggenhuizen, Tang, Xiao, Jin, Ding, Tang, Peng, Nie, Ao, Xiao, Zhong and Zhou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Xu, Jie
Shen, Chanjuan
Lin, Wei
Meng, Ting
Ooi, Joshua D.
Eggenhuizen, Peter J.
Tang, Rong
Xiao, Gong
Jin, Peng
Ding, Xiang
Tang, Yangshuo
Peng, Weisheng
Nie, Wannian
Ao, Xiang
Xiao, Xiangcheng
Zhong, Yong
Zhou, Qiaoling
Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients
title Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients
title_full Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients
title_fullStr Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients
title_full_unstemmed Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients
title_short Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients
title_sort single-cell profiling reveals transcriptional signatures and cell-cell crosstalk in anti-pla2r positive idiopathic membranous nephropathy patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202011/
https://www.ncbi.nlm.nih.gov/pubmed/34135910
http://dx.doi.org/10.3389/fimmu.2021.683330
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