Single-cell RNA sequencing of kidney from idiopathic membranous nephropathy patients
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ABSTRACT:
PROVIDER: PRJNA1007664 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25712264_1.fastq.gz | Fastqsanger.gz | |||
| SRR25712264_2.fastq.gz | Fastqsanger.gz | |||
| SRR25712265_1.fastq.gz | Fastqsanger.gz | |||
| SRR25712265_2.fastq.gz | Fastqsanger.gz | |||
| SRR25712266_1.fastq.gz | Fastqsanger.gz |
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Project description:Our understanding of the pathogenesis of idiopathic membranous nephropathy is limited by an incomplete molecular characterization of the cell types in the kidney and interaction between the cells. Besides, the reason for the heterogeneity of these patients as well as the variety of clinical outcomes remains elusive. Therefore, we applied scRNA-seq to kidney biopsies of patients with IMN to identify gene expression at the single-cell level, elucidate cells involved in the progression of IMN, and uncover intercellular interactions.
2021-05-30 | GSE171458 | GEO
Project description:Idiopathic membranous nephropathy and minimal change disease (MCD) transcriptome
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Project description:GWAS for Membranous Nephropathy
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Project description:The goal of the project was to identify risk alleles that are associated with recurrence of membranous nephropathy in the graft after kidney transplantation. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs.
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Project description:Introduction: Minimal change disease (MCD) is a major cause of nephrotic syndrome. With a substantial number of patients requiring long-term immunosuppression leading to significant morbidity, the study aim was to determine MCD glomerular transcriptome to serve as a basis for biomarker discovery and novel drug target identification. Animal work showed podocyte injury induced by IL-7/IL-7R signaling (Zhai S, BBRC, 2018). Methods: Renal biopsies from adult patients representing the following groups were selected from the Norwegian Kidney Biopsy Registry: MCD (n=14), as well as normal tissue (n=8) and primary membranous nephropathy (MN; n=12) as the two reference groups. RNA for 75 base-pair paired-end RNASeq was obtained by dissecting glomeruli via laser capture microdissection (LCM) from FFPE cross-sections. Systematic delineation of condition-specific alteration in transcriptional landscapes was achieved by combining pathway-centered analyses with methodologies derived from network science and integrating multiple bioinformatics resources. Results: Compared to normal glomeruli, glomeuli from MCD displayed an inflammatory signature that appeared to be predominantly governed by the IL1 and IL7 systems. While enrichment of IL1 production and secretion was a shared feature of MCD and MN compared to normal tissue, responses involving IL7 pathway activation were unique to MCD. Indeed, IL7R expressed by glomeruli was the most up-regulated gene of to the interleukin-family in MCD vs normal controls. IL7 pathway activation was paralleled by significant enrichment in adaptive immune system processes and transcriptional regulation and depletion in pathways related to energy metabolism and transcription. Downregulation of these organ function-related themes again occurred predominately in MDC and were significantly less pronounced in MN. Conclusion: Our results demonstrate that archival FFPE-biopsies can be used to generate glomeruli-specific gene expression profiles suitable for systematic delineation of kidney-associated diseases. Here the latter provides a data-driven rationale to experimentally address these MCD-specific features as biomarkers and as novel drug targets. In this context inhibiting activation of the IL7 pathway may be particularly promising.
2023-01-25 | GSE216841 | GEO
Project description:Single-cell profiling reveals transcriptional signatures, novel epithelial cells and cell-cell crosstalk in idiopathic membranous nephropathy patients
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Project description:Background: Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, the antigenic targets of disease are unknown for >10% of MN and >50% of membranous lupus nephritis (MLN) cases. We identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies through mass spectrometry (MS) of immune complexes recovered from biopsy tissue of patients with MN. Methods: MN cases negative for PLA2R, THSD7A, EXT1/2, and NELL1 were identified from a biopsy database. Protein G immunoprecipitation was used to recover immune complexes from frozen biopsy tissue, followed by interrogation by mass spectrometry (MS). Potential antigens were confirmed through paraffin immunofluorescence of protein targets, followed by co-localization with IgG within immune deposits. Consecutive series of 165 cases of PLA2R-negative MN biopsies and 95 MLN biopsies was screened to determine the frequency for each potential antigen. Results: Seven protein targets were discovered within immune complexes from MN biopsies including FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1, and VASN. Peptides from these proteins on MS were not enriched in PLA2R (n=86), THSD7A (n=64), NELL1 (n=64), or EXT1/2 (n=60) controls. Between 3-30 unique peptides were detected for each target. Frequencies of each antigen, determined by staining consecutive case series, were SEZ6L2 (1/165 idiopathic; 0/95 MLN), VASN (8/165 idiopathic; 2/95 MLN), EEA1 (6/165 idiopathic; 7/95 MLN), MST1 (6/165 idiopathic; 2/95 MLN), and FCN3 (0/165 idiopathic, 6/95 MLN), NPR3 and CD206 were positive in index cases. All cases showed co-localization of IgG within immune deposits. Conclusion: Seven novel protein targets were identified in MN and MLN.
2023-04-06 | PXD035854 | Pride
Project description:Background: Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, the antigenic targets of disease are unknown for >10% of MN and >50% of membranous lupus nephritis (MLN) cases. We identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies through mass spectrometry (MS) of immune complexes recovered from biopsy tissue of patients with MN. Methods: MN cases negative for PLA2R, THSD7A, EXT1/2, and NELL1 were identified from a biopsy database. Protein G immunoprecipitation was used to recover immune complexes from frozen biopsy tissue, followed by interrogation by mass spectrometry (MS). Potential antigens were confirmed through paraffin immunofluorescence of protein targets, followed by co-localization with IgG within immune deposits. Consecutive series of 165 cases of PLA2R-negative MN biopsies and 95 MLN biopsies was screened to determine the frequency for each potential antigen. Results: Seven protein targets were discovered within immune complexes from MN biopsies including FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1, and VASN. Peptides from these proteins on MS were not enriched in PLA2R (n=86), THSD7A (n=64), NELL1 (n=64), or EXT1/2 (n=60) controls. Between 3-30 unique peptides were detected for each target. Frequencies of each antigen, determined by staining consecutive case series, were SEZ6L2 (1/165 idiopathic; 0/95 MLN), VASN (8/165 idiopathic; 2/95 MLN), EEA1 (6/165 idiopathic; 7/95 MLN), MST1 (6/165 idiopathic; 2/95 MLN), and FCN3 (0/165 idiopathic, 6/95 MLN), NPR3 and CD206 were positive in index cases. All cases showed co-localization of IgG within immune deposits. Conclusion: Seven novel protein targets were identified in MN and MLN.
2023-04-06 | PXD035853 | Pride
Project description:Primary Membranous Nephropathy (PMN) is characterized by dysregulated immune responses, with B and T cells playing critical roles in disease pathogenesis. While significant strides have been made in identifying specific autoantigens and leveraging monoclonal antibodies, the precise immunopathogenic mechanisms underlying immune cell involvement in PMN remain elusive. To comprehensively characterize the cellular, molecular, and immunological landscape, we employed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cell samples (PBMC) obtained from 6 patients with PMN and 3 healthy controls (NC).We examined the heterogeneity and functional diversity of B cells in PMN. These results offer new insight into pathogenesis and identify new therapeutic targets for PMN.
2025-09-10 | GSE283826 | GEO