Project description:We recently developed a new model of renal agenesis [i.e., the heterogeneous stock derived model of unilateral renal agenesis, (HSRA)]. The HSRA model consistently exhibits unilateral renal agenesis ranging from 50-75% in each generation and is characterized by low nephron number, early kidney hypertrophy, and an inherent susceptibility to develop significant kidney injury and decline in renal function with age. Whole transcriptome analysis was evaluated at month 1 to identify early changes in genes/networks that may be involved in increased susceptibility of HSRA-S to develop kidney injury in the long-term.
Project description:We recently developed a new model of renal agenesis [i.e., the heterogeneous stock derived model of unilateral renal agenesis, (HSRA)]. The HSRA model consistently exhibits unilateral renal agenesis ranging from 50-75% in each generation and is characterized by low nephron number, early kidney hypertrophy, and an inherent susceptibility to develop significant kidney injury and decline in renal function with age. Whole transcriptome analysis was evaluated at month 1 to identify early changes in genes/networks that may be involved in increased susceptibility of HSRA-S to develop kidney injury in the long-term. An n=4 per group (independent samples) were evaluated for HSRA-S (congenital solitary kidney) and HSRA-C (two-kidney). HSRA-C (two-kidney) samples were set as the control.
Project description:Wt1 is required for renal development and homozyogus knockout mice show renal agenesis caused by apoptosis of the metanepric mesnchyme. To identify genes regulated by WT1, we performed comparative gene expression profiling on kidney rudmients of Wt1 heterozygous and homozygous mutant E10.25 embryos.
Project description:Renal oncocytomas are rare benign tumors of the kidney and are characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation. The abundance of proteins localized to mitochondria increased more than 2-fold, the only exception was a strong decrease in the abundance for CI subunits that revealed multiple pathogenic heteroplasmic mtDNA mutations by WES. We also observed renal oncocytomas to dysregulate main metabolic pathways, shunting away from gluconeogenesis and lipid metabolism. Nevertheless, the abundance of energy carrier molecules such as of NAD+, NADH, NADP, ATP and ADP were significantly higher in renal oncocytoma. Finally, a tremendous 5000-fold increase of the reactive oxygen species (ROS) scavenger glutathione (GSH) can be regarded as a new hallmark of renal oncocytoma. Our findings demonstrate that renal oncocytomas undergo a metabolic switch to eliminate ATP consuming processes to ensure a sufficient energy supply for the tumor.
Project description:Transcriptional profiling of Embryonic Day 14.5 mouse kidneys comparing the infuence of gestational high salt stress on gene expression remolding of BdkrB2 receptor null mice with that of BdkrB2 receptor wild type mice. The BdkrB2 receptor has been shown to be playing a role in renal vascular tone, kidney secretion and reabsorption function, normal kidney development, while impaired BdkrB2 receptor in kidney shown being associated with renal agenesis and renal dysplasia. Goal was to determine the effects of BdkrB2 receptor knockout together with gestational high salt stress on renal gene expression pattern.
Project description:Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome marked by haploinsufficiency of genes in chromosomal region 11p11.2p12. Approximately 50 cases of PSS have been reported; however, a syndrome with a PSS-like clinical phenotype caused by 11p11.12p12 duplication has not yet been reported. We first report the 11p11.12p12 duplication in a family with intellectual disability and craniofacial anomalies. 11p11.12p12 duplication syndrome was identified by karyotype analysis. Next-generation sequencing (NGS) analysis clarified the location of the chromosomal variations, which was confirmed by chromosome microarray analysis (CMA). Whole-exome sequencing (WES) was performed to exclude single nucleotide variations (SNVs). The raw data of NGS analysis and WES have been submitted to SRA, the accession number is PRJNA713823.
Project description:Wt1 is required for renal development and homozyogus knockout mice show renal agenesis caused by apoptosis of the metanepric mesnchyme. To identify genes regulated by WT1, we performed comparative gene expression profiling on kidney rudmients of Wt1 heterozygous and homozygous mutant E10.25 embryos. To identify deregulated genes, timed matings were performed and embryos isolated at E10.25, a time point before the onset of apoptosis in Wt1 mutants. The region containing the metanephric mesenchyme was microdissected, RNA isolated and after labeling, hybridized to Mouse Genome Survey Microarrays. Deregulated genes were identified using GeneSpring (GSX) software.
Project description:Bilateral renal cell carcinoma (RCC) is a rare type of this disease and includes familial bilateral and sporadic bilateral RCCs. Studying the cellular molecular characteristics of sporadic bilateral is important to provide a direct guide for clinical treatment. These cellular molecular characteristics can be expressed at the RNA level, especially at the single-cell RNA level. Single-cell RNA sequencing (scRNA-seq) was performed on bilateral clear cell RCC (ccRCC). A total of 3,575 and 3,568 high-quality single-cell transcriptome data were captured from the left and right tumour tissues, respectively. Gene characteristics were identified by comparing left and right tumours at the scRNA level. This work presented the complex cellular environment of bilateral ccRCC by scRNA-seq. Single-cell transcriptome analysis revealed high similarity in gene expression among most cell types of bilateral RCCs but significant differences in gene expression among different site tumour cells. Additionally, the potential biological function of different tumour cell types was determined by gene ontology (GO) analysis. The transcriptome characteristics of tumour tissues in different locations at the single-cell transcriptome level were revealed through the scRNA-seq of bilateral sporadic ccRCC. This work provides new insights into the diagnosis and treatment of bilateral RCC.