CosMx 6175 human gene for human kidney primary non-function and immediate graft function.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1186679 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This dataset includes CosMx spatial transcriptomic data from human kidney biopsies collected one hour post-transplantation. Patients were then monitored and categorized into two groups: immediate graft function (IGF) and primary nonfunction (PNF). PNF refers to cases where the transplanted kidney never functions. The biopsies were formalin-fixed, paraffin-embedded, and sectioned using a microtome. Sample processing followed NanoString's standard protocol, utilizing a pre-made 6,175-gene panel to detect the spatial location and expression levels of each gene, without any additional custom probes.
2024-11-29 | GSE282026 | GEO
Project description:The frequency of delayed function of kidney transplants varies greatly and is associated with the quality of graft, donor age, and the duration of cold ischemia time. Body weight differences between donor and recipient can affect primary graft function. The underlying mechanism is poorly understood. Here, we have transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. 24 hours post-transplantation, serum creatinine level in H-WD recipients was significantly higher compared to that of L-WD recipients indicating impaired primary graft function. We detected a 10 fold higher transcription of IL-6 and dramatically increased tubular destruction in grafts from H-WD recipients. This was accompanied by decreased expression of genes associated with kidney function and an up-regulation of other genes such as cytochrome P450 isoforms, FosL and Trib3 as revealed by DNA microarray analysis. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and to cause tubular damage. Whereas, immediate neutralization of IL-6 receptor signaling rescued primary graft function resulting in low serum creatinine levels, well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function. The dataset comprises eight samples divided into four sample groups. Each group represents rat kidneys collected after allogeneic transplantation under a certain condition and includes two biological replicates. The first group is characterized by a high body weight difference between donor and recipient, rats in the second group exhibit a low weight difference. Group three and four are similar to group one, but underwent an additional treatment with anti-IL6R mAb or prednisolone immediately after transplantation.
2010-04-08 | E-GEOD-15813 | biostudies-arrayexpress
Project description:The frequency of delayed function of kidney transplants varies greatly and is associated with the quality of graft, donor age, and the duration of cold ischemia time. Body weight differences between donor and recipient can affect primary graft function. The underlying mechanism is poorly understood. Here, we have transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. 24 hours post-transplantation, serum creatinine level in H-WD recipients was significantly higher compared to that of L-WD recipients indicating impaired primary graft function. We detected a 10 fold higher transcription of IL-6 and dramatically increased tubular destruction in grafts from H-WD recipients. This was accompanied by decreased expression of genes associated with kidney function and an up-regulation of other genes such as cytochrome P450 isoforms, FosL and Trib3 as revealed by DNA microarray analysis. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and to cause tubular damage. Whereas, immediate neutralization of IL-6 receptor signaling rescued primary graft function resulting in low serum creatinine levels, well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function.
2009-07-22 | GSE15813 | GEO
Project description:Delayed graft function (DGF) is associated with a reduced graft survival. Donors' features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the role of recipients' characteristics in the development of DGF. We prospectively enrolled 932 kidney graft recipients from 466 donors. A total of 226 recipients experienced DGF. Among the 466 donors, in 290 both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B) and in 126 one recipient presented with DGF and the other with EGF (group C). In group C we randomly selected 7 couples of DGF/EGF recipients. In these patients, circulating mononuclear cells were harvested before transplantation and their transcriptomic profile was investigated by a microarray approach. Results were validated by qPCR in an independent group of EGF/DGF couples.
2022-12-22 | E-MTAB-10747 | biostudies-arrayexpress
Project description:Delayed graft function (DGF) is commonly defined as dialysis in the first week post-transplant. This definition, though readily applicable, is too generic and unable to distinguish between “types� of DGF or time needed to recover function. We aimed to profile biological pathways in DCD kidney donors that correlate with DGF and discriminate different durations. N=30 DCD kidney biopsies were selected from the UK Quality in Organ Donation biobank and stratified according to DGF duration (immediate function, IF n=10; “short-DGF� (1-6 days), SDGF n=10; “long-DGF� (7-22 days), LDGF n=10). Samples were matched for donor and recipient demographics and analysed by label-free quantitative proteomics, yielding identification of N=3,378 proteins. Ingenuity Pathway Analysis on differentially abundant proteins showed that SDGF kidneys presented stress response pathways upregulation, while LDGF presented impaired response to stress, compared to IF. LDGF showed extensive metabolic deficits compared to IF and SDGF. DCD kidneys requiring dialysis only in the first week post-transplant present acute cellular injury at donation, alongside repair pathways upregulation. In contrast, DCD kidneys requiring dialysis longer beyond 7 days present minimal metabolic and antioxidant responses, suggesting current DGF definitions might not be adequate in distinguishing different types of injury in the donor kidneys contributing to DGF.
2024-05-23 | PXD038196 | Pride
Project description:A Molecular signature for Delayed Graft Function
| PRJNA356242 | ENA
Project description:Delayed graft function (DGF) is associated with a reduced long-term graft survival. Ischemia-reperfusion damage and donors' features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the role of recipients' characteristics in the development of DGF to discover early genomics biomarkers in peripheral blood mononuclear cells (PBMC) in order to identify patients at risk. We prospectively enrolled 932 kidney graft recipients from 466 donors for both kidneys. A total of 226 recipients experienced DGF. Among the 466 donors, 290 couples of recipients both patients presented with early graft function (EGF, group A), 50 couples experienced DGF (group B) and 126 couples of recipients were discordant as one presented DGF and the other promptly recovered graft function (group C). In group C we randomly selected 10 couples of DGF/EGF recipients. Peripheral blood mononuclear cells (PBMC) were harvested before transplantation; their transcriptomic profile was investigated by a microarray approach and microarray results were validated by qPCR in an independent group (DGF n=25; EGF n=25). In the whole study group, DGF was independently associated with both donors’ and recipient’s features. Moreover, group A, B and C presented significant differences in both donors’ and recipients’ characteristics. In group C of patients, DGF was significantly associated with body mass index, dialysis modality and number of mismatches. Two-hundred and seventy-three genes were differentially expressed before transplantation in discordant EGF/DGF patients of group C. Their main biological functions were immune dysfunction and inflammation. Among the differentially expressed genes, we observed a significant increase in the expression of CCR2, the MCP-1 receptor, in DGF patients. CCR-2 and MCP-1 up-regulation was confirmed in an independent cohort of patients. Our results suggest that recipients' clinical and immunological features, potentially modulated by dialysis modality, are associated with the development of DGF independently of donors' features.
2022-10-01 | GSE159636 | GEO
Project description:Kidney failure, the decrease of kidney function below a threshold necessary to support life, is a major cause of morbidity and mortality in humans. Kidney function is highly heritable; yet, the cellular and molecular mechanisms which contribute to differences in human kidney function remain obscure. We performed a genome wide association study (GWAS), identifying 430 loci affecting kidney function in middle-aged adults. To investigate which cell types are affected by these loci, we integrated the GWAS with human kidney candidate cis-regulatory elements (cCREs), identified using scATAC-seq. 56% of kidney function heritability localized to kidney tubule epithelial cCREs and an additional 7% to kidney podocyte cCREs. Thus, most of the heritable differences in adult kidney function is due to altered gene expression in these two cell types. Using enhancer assays, allele-specific scATAC-seq and machine learning, we found that many kidney function variants alter cCRE chromatin accessibility and function. Using CRISPRi, we determined which genes some of these cCREs regulate, implicating NDRG1, CCNB1 and STC1 in human kidney function. This work provides an experimental approach to identify the variants, regulatory elements and genes involved in human traits and disease.
2024-07-15 | GSE266319 | GEO
Project description:Donor organ shortage, growing waiting lists and organ discard rates are key problems in kidney transplantation. Donor organ quality is a critical factor determining post-transplant graft outcomes. However, organ quality is difficult to predict. Balancing the use of marginal donors without affecting outcomes is a main issue in the transplant field. The decision of acceptance of a kidney organ for transplantation is mainly based on donor organ biopsy findings, even though there are recognized limitations. The lack of better measures of organ quality at the time of transplantation as a predictor of performance graft outcome is a serious clinical challenge. Herein, we propose the use of a limited set of genes that captures intrinsic biology of kidney donor organs to improve available scoring systems. We studied gene expression in 192 deceased donor kidney biopsies and evaluated short-term outcomes which included delayed graft function and eGFR (high versus low) at 24 months for 168 kidney transplant recipients.
2022-06-13 | GSE147451 | GEO
Project description:Survival of solid organ grafts depends on life-long immunosuppression, which results in increased rates of infection and malignancy. Induction of tolerance to allografts would represent the optimal solution for controlling both chronic rejection (CR) and side effects of immunosuppression. Although spontaneous ‘‘operational tolerance’’ can occur in human kidney transplantation, the lack of noninvasive peripheral blood biological markers of this rare phenomenon precludes the identification of potentially tolerant patients in whom immunosuppression could be tapered as well as the development of new tolerance inducing strategies. Here, the potential of high throughput microarray technology to decipher complex pathologies allowed us to study the peripheral blood specific gene expression profile and corresponding EASE molecular pathways associated to operational tolerance in a cohort of human kidney graft recipients. In comparison with patients with CR, tolerant patients displayed a set of 343 differentially expressed genes, mainly immune and defense genes, in their peripheral blood mononuclear cells (PBMC), of which 223 were also different from healthy volunteers. Using the expression pattern of these 343 genes, we were able to classify correctly >80% of the patients in a cross-validation experiment and classified correctly all of the samples over time. Collectively, this study identifies a unique PBMC gene signature associated with human operational tolerance in kidney transplantation. 250 samples were analyzed, replicates included: some patients from the TOL and CR groups were sampled twice with an interval between the two different time points of at least 16 months (mean 25.8 months, range 16–31 months). All the samples were analyzed in duplicate or quadruplicate. 1. TOL (n = 21). patients with stable graft function (blood creatinemia<150 mmol/L, proteinuria<1 g/24 h) for at least 1 year (mean 6.4 years,range 1.6–17.2 years) after complete interruption of immunosuppressive therapy. 2. STA (n = 190). Patients with stable kidney graft function under immunosuppressive therapy. 3. CR (n = 31). Patients having a progressive degradation of their renal function (blood creatinemia ≥150 mmol/L, proteinuria ≥1 g/24 h). CR was diagnosed on a graft biopsy according to the updated Banff criteria. CR was defined by histological signs of chronic allograft arteriopathy (arterial intimal fibrosis with mononuclear cell infiltration) and/or transplant glomerulopathy with glomerular double contours. 4. HV (n = 8). Subjects having normal blood formulae and no infectious or other concomitant pathology for at least 6 months before the study.
2017-02-09 | GSE47755 | GEO