Single Nuclei Transcriptomics Delineates Complex Interactions Between Immune and Renal Cells Contributing to Kidney Graft Fibrosis
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ABSTRACT:
PROVIDER: PRJNA802013 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17830031_1.fastq.gz | Fastqsanger.gz | |||
| SRR17830031_2.fastq.gz | Fastqsanger.gz | |||
| SRR17830032_1.fastq.gz | Fastqsanger.gz | |||
| SRR17830032_2.fastq.gz | Fastqsanger.gz | |||
| SRR17830033_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Chronic allograft dysfunction (CAD) remains a major obstacle in kidney transplantation. However, the molecular pathogenesis of human CAD is unknown. Herein, we tested the hypothesis that single nuclei transcriptomics of human kidney allograft fibrosis will reveal diverse cell types, deconvolve complex fibrosis-driving pathways, and provide deeper insights into the progression of kidney allograft dysfunction.
2023-03-06 | GSE195718 | GEO
Project description:The significance of borderline changes (BL) in kidney allograft biopsies is widely debated. We examined differences in gene expression patterns between early clinical biopsy tissue and 3-month protocol biopsy tissue, all of which had histological BL changes and identified specific molecular BL patterns associated with poor graft outcome. The expression profiles were analyzed in training set of patients and next data were validated in validation cohort using RT-qPCR. Using the Illumina microarray technology, we observed greater expression of immunity- and inflammation-related genes in tissues from early clinical biopsies compared to 3-month protocol biopsies with BL findings. In tissues with early clinically manifested BL changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes, specifically with higher donor age and expression of macrophage receptor CLEC5A. In the 3-month protocol biopsies with BL changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. This study highlights the molecular differences between clinical and subclinical biopsies with similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those who received grafts from expanded criteria donors (ECDs). The experiments were performed with total RNA derived from the renal graft biopsy samples of 28 different patients who had undergone a kidney transplantation. Only the patients with diagnosis of borderline changes early (M-bM-^IM-$2 months) or protocolar (3 months) were included in the study. RNA profiles of patients with stable and deteriorated graft function during 2 years after transplantation were compared. As microarray platform, Illumina HumanHT-12 v4.0 Expression BeadChips (Illumina) was used. The chip scanning was performed with a BeadStation 500 instrument (Illumina Inc), and the raw data were extracted with the BeadStudio Data Analysis Software (Illumina). The R software lumi package was used to further process the raw data. The quantile method was used for normalization.
2013-12-19 | E-GEOD-52694 | biostudies-arrayexpress
Project description:Intragraft transcriptional profiles were investigated in patients with tubular dysfunction to disclose subclinical mechanisms underlying graft deterioration. Moreover, we analyzed whether individualization of immunosuppression could modify this profile while improving renal function after 12 months of regimen modification.
2015-07-31 | GSE48250 | GEO
Project description:The mesothelium forms epithelial membranes that line the bodies cavities and surround the internal organs. Mesothelia widely contribute to organ homeostasis and regeneration, and their dysregulation can result in congenital anomalies of the viscera, ventral wall defects, and mesothelioma tumors. Nonetheless, the embryonic ontogeny and developmental regulation of mesothelium formation has remained uncharted. Here, we combine genetic lineage tracing, in toto live imaging, and single-cell transcriptomics in zebrafish to track mesothelial progenitor origins from the lateral plate mesoderm (LPM). Our single-cell analysis uncovers a post-gastrulation gene expression signature centered on hand2 that delineates distinct progenitor populations within the forming LPM. Combining gene expression analysis and imaging of transgenic reporter zebrafish embryos, we chart the origin of mesothelial progenitors to the lateral-most, hand2-expressing LPM and confirm evolutionary conservation in mouse. Our time-lapse imaging of transgenic hand2 reporter embryos captures zebrafish mesothelium formation, documenting the coordinated cell movements that form pericardium and visceral and parietal peritoneum. We establish that the primordial germ cells migrate associated with the forming mesothelium as ventral migration boundary. Functionally, hand2 mutants fail to close the ventral mesothelium due to perturbed migration of mesothelium progenitors. Analyzing mouse and human mesothelioma tumors hypothesized to emerge from transformed mesothelium, we find de novo expression of LPM-associated transcription factors, and in particular of Hand2, indicating the re-initiation of a developmental transcriptional program in mesothelioma. Taken together, our work outlines a genetic and developmental signature of mesothelial origins centered around Hand2, contributing to our understanding of mesothelial pathologies and mesothelioma.
2022-01-14 | E-MTAB-9727 | biostudies-arrayexpress
Project description:The significance of borderline changes (BL) in kidney allograft biopsies is widely debated. We examined differences in gene expression patterns between early clinical biopsy tissue and 3-month protocol biopsy tissue, all of which had histological BL changes and identified specific molecular BL patterns associated with poor graft outcome. The expression profiles were analyzed in training set of patients and next data were validated in validation cohort using RT-qPCR. Using the Illumina microarray technology, we observed greater expression of immunity- and inflammation-related genes in tissues from early clinical biopsies compared to 3-month protocol biopsies with BL findings. In tissues with early clinically manifested BL changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes, specifically with higher donor age and expression of macrophage receptor CLEC5A. In the 3-month protocol biopsies with BL changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. This study highlights the molecular differences between clinical and subclinical biopsies with similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those who received grafts from expanded criteria donors (ECDs).
2013-12-19 | GSE52694 | GEO
Project description:Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. While previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on VGF. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing (snRNA-seq) and spatial transcriptomics (ST) analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-cartoid vein bypass implantation in a canine model (n=4). Collectively, we find that vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies.
2024-05-29 | GSE263280 | GEO
Project description:To assess the preclinical utility and functional mechanism of intraperitoneal anti-CX3CL1 mAb therapy in the skin and lung fibrosis, sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) model mice were analyzed by RNA-sequencing assays.
2024-05-03 | GSE227285 | GEO
Project description:Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pre-transplant molecular markers for predicting PGD. To identify distinctive gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to the graft implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD. Matched factors used were: recipient age (± 10 years), recipient gender, recipient lung disease, and type of transplantation (single or bilateral). Keywords: Observational case-control study Matched case-control observational study: 10 primary graft dysfunction cases vs 16 Good outcome cases. One replicate per array.
2008-09-15 | E-GEOD-9102 | biostudies-arrayexpress
Project description:Background: The mechanisms underlying fat graft survival are poorly understood. Here, we performed unbiased transcriptomics analysis of mouse fat graft model to find out the molecular mechanism of free fat graft survival. Methods: We conducted RNA-sequencing (RNA-seq) analysis of mouse free subcutaneous fat graft model at day 3 and 7 following grafting (n=5). High-throughput sequencing was performed as paired-end using NovaSeq6000 (Illumina, CA, USA). The calculated transcripts per million (TPM) values were processed for principal component analysis (PCA), unsupervised hierarchically clustered heat map generation, and Gene set enrichment analysis. Results: PCA and heat map data revealed global differences in the transcriptome of grafted fat when compared with non-graft control. The top meaningful up-regulated gene sets in the grafted fat were related to epithelial mesenchymal transition and hypoxia by day 3, and angiogenesis by day 7. Mechanistically, the glycolysis pathway was commonly upregulated in the grafted fat at day 3 (FDR q=0.012) and day 7 (FDR q=0.084). In subsequent experiments, pharmacological inhibition of glycolytic pathway in the grafted fat with 2-Deoxy-D-glucose (2-DG) significantly suppressed fat graft retention rates, both grossly and microscopically (n=5). Conclusions: Global transcriptome analysis and pharmacologic inhibition study revealed that free adipose tissue grafts undergo metabolic reprogramming towards glycolytic pathway. Whether targeting the pathway wound enhance graft survival rate remains to be investigated.
2024-06-01 | GSE203599 | GEO