Project description:Diabetic nephropathy is a chronic complication of diabetes, presenting albuminuria at an early stage and leading to renal failure. Kidney is a complicated organ, which is responsible for body fluids control, acid-base balance, and removal of toxins. To better understand the progress of diabetic nephropathy, mice renal cortex of control mice, six-week db-/- (increased serum glucose without pathological changes in kidneys), and ten-week db-/- (with pathological changes in kidneys) were collected for single-cell sequencing analyses. A subgroup of glomerular endothelial cells with pro-angiogenetic features was identified in diabetic kidneys.
Project description:The raw proteomics data in the manuscript “Single-cell RNA-sequence reveals that the switching of the transcriptional profiles of cysteine-related genes alter the virulence of Entamoeba histolytica”
Project description:Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease worldwide. Susceptibility to DN is inherited but genetic determinants of DN have not been precisely defined. We have previously described a mouse model combining genetic type 1 diabetes (Akita) with a renin transgene (ReninTg) that exhibits characteristic features of human DN including albuminuria, glomerulosclerosis, and genetic predisposition for kidney disease. We performed single-cell sequencing (10x Chromium) of glomerular cell suspensions obtained from the wildtype (WT) and Akita- ReninTg (AR) mice at 10 weeks of age before overt pathological abnormalities are present in kdiney.
Project description:IgA nephropathy represents the most prevalent chronic nephrosis worldwide. However, pathogenesis about IgA deposition and end-stage renal failure is still not well defined. Using single-cell RNA-seq, we identified the mesangial membrane receptor for IgA, which collaborates with increased extracellular matrix proteins and protease inhibitor to facilitate IgA deposition. Meanwhile, cell-cell interaction analysis revealed increased communications between mesangium and other cell types, uncovering how morbidity inside glomerulus spreads to whole kidney, which results in the genetic changes of kidney resident immune cells. Prominent interaction decreasing in intercalated cells leads to the discovery of a transitional cell type, which exhibited significant EMT and fibrosis features. Our work comprehensively characterized the pathological mesangial signatures, highlighting the step-by-step pathogenic process of IgA nephropathy from mesangium to epithelium.
Project description:Mouse models have been widely used to understand kidney disease pathomechanisms and play an important role in drug discovery. However, these models have not been systematically analyzed and compared. We analyzed single-cell RNA sequencing data (36 samples) and bulk gene expression data (42 samples) from 18 commonly used mouse kidney disease models. We compared single-nucleus RNA sequencing data from a mouse diabetic kidney disease model with data from patients with diabetic kidney disease and healthy controls. We generated a uniformly processed mouse single-cell atlas containing information for nearly 300,000 cells, identifying all major kidney cell types and states. Our analysis revealed that changes in fractions of cell types are major drivers of differences in bulk gene expression. Although gene expression changes at the single-cell level were mostly model-specific, different disease models showed similar changes when compared at a pathway level. Tensor decomposition analysis highlighted the important changes in proximal tubule cells in disease states. Specifically, we identified important alterations in expression of metabolic and inflammation-associated pathways. The mouse diabetic kidney disease model and patients with diabetic kidney disease shared only a small number of conserved cell type-specific differentially expressed genes, but we observed pathway-level activation patterns conserved between mouse and human diabetic kidney disease samples. This study provides a comprehensive mouse kidney single-cell atlas and defines gene expression commonalities and differences in disease states in mice. The results highlight the key role of cell heterogeneity in driving changes in bulk gene expression and the limited overlap of single-cell gene expression changes between animal models and patients, but they also reveal consistent pathway-level changes.
Project description:Kidney aging is an irreversible physiological process and some suggest that kidney aging is viewed as a pathological condition. To enhance understanding of the molecular nature of renal aging, we performed whole kidney RNA sequencing in young mice (2-month-old) fed with standard diet versus those with adenine-enriched diet, and this bulk transcriptome was then compared with transcriptional changes with aging.
Project description:Single RNA sequencing analysis of myosin binding protein C3 (mybpc-3) associated Hypertrophic Cardiomyopathy to identify single cell gene expression changes across common pathological mechanisms and species-specific distinctions in human, feline, and murine heart tissues.
Project description:Current renal organoid models derived from embryonic or induced pluripotent stem cells mimic development. Yet, few studies have attempted to generate organoids from human adult kidney to recapitulate regeneration or pathological dysregulation in vitro. Here, we report a novel expanding regenerative organoids culture system from renal cortex and medulla. Transcriptomic sequencing and immunostaining identified that these organoids share similar molecular features with kidney injury-responsive regeneration. Heterogeneous populations in organoids including cycling epithelial progenitors and differentiated cell types were identified by single cell sequencing including proximal tubules, principal cells and collecting duct (CD) progenitors that can be induced into functional CD system. Furthermore, we established polycystic organoids derived from patients that represent an advanced platform for polycystic kidney disease (PKD) modeling. By drug screening, QNZ, GSK2193874 and AMPK activators were shown to significantly reduce polycystic growth. Our results demonstrated a novel in vitro renal organoid model to study regenerating adult renal cells and PKD mechanism, providing tools for discovery of therapeutic targets.
Project description:Current renal organoid models derived from embryonic or induced pluripotent stem cells mimic development. Yet, few studies have attempted to generate organoids from human adult kidney to recapitulate regeneration or pathological dysregulation in vitro. Here, we report a novel expanding regenerative organoids culture system from renal cortex and medulla. Transcriptomic sequencing and immunostaining identified that these organoids share similar molecular features with kidney injury-responsive regeneration. Heterogeneous populations in organoids including cycling epithelial progenitors and differentiated cell types were identified by single cell sequencing including proximal tubules, principal cells and collecting duct (CD) progenitors that can be induced into functional CD system. Furthermore, we established polycystic organoids derived from patients that represent an advanced platform for polycystic kidney disease (PKD) modeling. By drug screening, QNZ, GSK2193874 and AMPK activators were shown to significantly reduce polycystic growth. Our results demonstrated a novel in vitro renal organoid model to study regenerating adult renal cells and PKD mechanism, providing tools for discovery of therapeutic targets.