Project description:The Illumina Infinium MethylationEPIC Beadchip was used to obtain genomewide methylation profiles from Human Urine Renal Progenitors obtained after kidney transplantation from lived donors or dead donors
Project description:Kidney transplantation is the treatment of choice for patients with end-stage chronic kidney disease (ESKD). Despite the usefulness of transplantation as replacement therapy, long-term graft survival represents a major challenge for transplant immunology. Although nowadays there has been an advance in understanding immunological mechanisms mediating rejection, and the improvement of immunomodulation therapies, there are still underlying molecular processes marking an important variability among patients, and presumably influencing allograft rejection. With our analysis we explored differences in gene expression by Next Generation Sequencing implementing RNA-Seq in biopsies, blood and urine from kidney transplant patients with acute and chronic rejection. For this, we performed an intra-outcome analysis simultaneously in acute and chronic rejection, with which we sought: 1. To identify differences in gene expression between peripheral blood vs renal tissue and peripheral blood vs urine in acute rejection and chronic rejection; 2. To identify the level of agreement in gene expression between renal tissue and urine in acute rejection and chronic rejection and 3. To identify genes and biological processes associated with acute rejection and chronic rejection that could be potentially detected in blood, and simultaneously in urine and biopsy in acute rejection and in chronic rejection.
Project description:We characterized the transcriptome and methylome of renal progenitor cells in the urine of a cohort of stable kidney transplant recipients to elucidate whether the origin of the donor (living or deceased donor) was associated with a specific molecular reprogramming.
Project description:This study represents the first quantitative analysis of the temporal changes in the small urinary extracellular vesicle proteome throughout living donor kidney transplantation identifying PCK2 abundance as a biomarker for renal function 12 months after transplantation
Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that progenitor cells can be cloned from mouse medulla and cortex. Clones can be grown from a single cell and indefinitely passaged. Progenitor cells derived from renal medulla can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.
Project description:The study comprises various components: Samples TD: We aims to screen out different gene expression profile in donor biopsies after revascularization , We aims to predict renal allograft dysfunction early after transplantation. Samples AR, ATN, Tx: We aim to screen out different gene expression profile in acute rejection on the kidney. We aim to screen out different gene expression profile in acute tubular necrosis on the kidney. Results from the various study components can help to diagnose renal allograft dysfunction with different causes by distinct gene expression profile. Keywords: acute rejection, acute tubular necrosis, donor biopsies, renal allograft dysfunction Samples AR1-AR17: This study has been accomplished with 17 patients of acute rejection on the kidney.Technical replicates: 2 replicates Samples ATN1-ATN5: This study has been accomplished with 5 patients of acute tubular necrosis on the kidney. Technical replicates: 2 replicates Samples Tx1-Tx14: This study has been accomplished with 14 patients of stable renal function on the kidney.Tecnical replicates:2 replicates(except Tx12) Samples TD1-TD12: This study has been accomplished with 12 patients of donor tissue with stable function early after transplantation on the kidney.Technical replicates: 2 replicates Samples TD13-TD21: This study has been accomplished with 9 patients of donor tissue with renal dysfunction early after transplantation on the kidney.Technical replicates: 2 replicates
Project description:Early diagnosis and treatment is pivotal to the management of kidney disease, whereas the pathological mechanisms and minimally invasive diagnostic method still need to be investigated. In the present study, single-cell RNA sequencing (scRNA-seq) was used to evaluate the heterogeneity of kidney diseases in single cell level. Cellular gene expression profiles of cells of renal tissue, peripheral blood mononuclear cells (PBMCs) and urine from four nephritis patients were performed. Our analysis revealed 12 subsets of renal cells and leukocytes, including fibroblast cells, mesangial cells, epithelial cells, proximal tubule cells (PTCs), and 6 types of immune cells, CD8+ T cell, macrophages (MC), nature killer cells (NK), dendritic cells (DC), B cell and neutrophils. PTCs were detected in both PBMC and urine, while PTC was negative in healthy blood sample. Multiple populations of fibroblast cells, mesangial cells and PTCs demonstrated pro-inflammatory or pro-apoptotic responses. Gene expression analysis suggested that chemotactic and activating effect of inflammatory PTCs and fibroblasts on neutropils were critical for the development and progress of nephritis, which was supported by the widely overexpressed pro-inflammatory genes in these cells. Gene expression profiles of inflammatory PTCs in PBMC, urine and kidney are highly correlated, indicating the high possibility of urine and PBMC PTCs in serving as a surrogate for kidney biopsies.