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Developing a novel human adult kidney organoid model to recapitulate injury-associated regeneration and polycystic kidney disease [RNA-Seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228971 | GEO | 2023/08/28

REPOSITORIES: GEO

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Developing a novel human adult kidney organoid model to recapitulate injury-associated regeneration and polycystic kidney disease [scRNA-Seq]

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.

2023-08-31 | GSE241972 | GEO

Expression data from kidney of 36d old PKD/Mhm rats.

2009-09-30 | GSE13065 | GEO

Transcription profiling of rat kidney from male and female heterozygous PKD/Mhm and wild type animals

Project description:Gender has strong impact on kidney performance. Female gender tends to be renal protective. PKD/Mhm is rat model for human polycystic kidney disease (PKD) caused by a mutation in gene Anks6. PKD progresses faster in male rats compared with females. We used microarrays to detect gender-dependent gene expression in kidney of 36d old PKD/Mhm rats. Experiment Overall Design: Gender-dependent gene expression was examined both in heterozygous PKD/Mhm rats affected with PKD and in their wild type littermates. Three microarrays were hybridized for each combination of gender and genotype.

2009-10-11 | E-GEOD-13065 | biostudies-arrayexpress

Untargeted gas chromatography–mass spectrometry-based metabolomics analysis of kidney and liver tissue from the Lewis Polycystic Kidney rat

Project description:Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments. The Lewis Polycystic Kidney (LPK) rat phenotype has been characterized and classified as a model of nephronophthisis (NPHP9, caused by mutation of the Nek8 gene) for which polycystic kidneys are one of the main pathologic features. The aim of this study was to use a GC-MS-based untargeted metabolomics approach to determine key biochemical changes in kidney and liver tissue of the LPK rat. Tissues from 16-week old LPK (n = 10) and Lewis age- and sex-matched control animals (n = 11) were used. Principal component analysis (PCA) distinguished signal corrected metabolite profiles from Lewis and LPK rats for kidney (PC-1 77%) and liver (PC-1 46%) tissue. There were marked differences in the metabolite profiles of the kidney tissues with 122 deconvoluted features significantly different between the LPK and Lewis strains. The metabolite profiles were less marked between strains for liver samples with 30 features significantly different. Five biochemical pathways showed three or more significantly altered metabolites: transcription/translation, arginine and proline metabolism, alpha-linolenic and linoleic acid metabolism, the citric acid cycle, and the urea cycle. The results of this study validate and complement the current literature and are consistent with the understood pathobiology of PKD.

2023-01-26 | MTBLS748 | MetaboLights

Polycystic Kidney Disease Progression Expression Analysis

Project description:Polycystic Kidney Disease (PKD) is a genetic disease of the kidney characterized by the gradual replacement of normal kidney parenchyma by fluid-filled cysts and fibrotic tissue. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene. Here we present an RNASeq experiment designed to investigate the effect of a kidney specific and Tamoxifen inducible knockout of the Pkd1 gene in mice. The Pkd1cko mice were harvested at different time points 2-weeks, 3-weeks, 5-weeks, 10.5-weeks, 11-weeks and 15-weeks after gene inactivation.

2019-12-24 | E-MTAB-8086 | biostudies-arrayexpress

Expression profiling of Pkd1cko mice: A model of Polycystic Kidney Disease

Project description:Polycystic Kidney Disease (PKD) is a genetic disease of the kidney characterized by the gradual replacement of normal kidney parenchyma by fluid-filled cysts and fibrotic tissue. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene. Here we present an RNASeq experiment designed to investigate the effect of a kidney specific and Tamoxifen inducible knockout of the Pkd1 gene in mice. 7 mice were grouped into two groups, 4 Tamoxifen treated mice which develop an adult onset Polycystic Kidney Disease phenotype and 3 untreated mice which have WT phenotype.

2016-06-01 | E-MTAB-4086 | biostudies-arrayexpress

Regulation of gene expression by GLIS3 during neonatal kidney development

Project description:Loss of transcription factor GLIS3 function in humans and mice leads to the development of neonatal polycystic kidney disease (PKD). To investigate how loss of GLIS3 function in kidney affects postnatal kidney development and PKD, we analyzed the gene expression profiles of kidneys from WT and Glis3-null mice at P7, P14, and P28 by RNA-Seq analysis using Glis3 global KO model Glis3-mCherry and kidney specific knockout model Glis3-PAX8Cre.

2023-12-31 | GSE240071 | GEO

Establishment of epithelial inflammatory injury model using adult kidney organoids [scRNA-seq]

Project description:Kidney organoids are emerging as an increasingly applied model system to hold great promise for transplantation to individuals with end-stage renal disease and as a useful tool for kidney research. Multiple iPSC-derived renal organoids have been established to understand kidney development and disease. However, few disease models originated from adult renal tissue with fully mature cell fates have been set up to recapitulate kidney inflammation or fibrosis. Here we created a novel organoid model that faithfully representing the cellular state of inflammatory response during the progression of renal disease upon TNFα exposure. scRNA-seq showed signatured inflammatory chemokines, cytokines and inflammation-associated signaling pathways were activated in TNFα-treatment organoids together with injury-associated markers such as LCN2 and CLU. Donor age is associated with TNFα-induced inflammatory reaction in organoids. Kidney organoids from young donors showed more transcriptional changes by down-regulation of TGFβ and extracellular matrix genes. In summary, we established an in vitro TNFα-treated kidney organoid model that representing the cellular state of the inflammatory response during renal disease progression and provided a novel tool for studying inflammation-related kidney disease and drug discovery.

2024-03-03 | GSE259381 | GEO

Establishment of epithelial inflammatory injury model using adult kidney organoids [RNA-seq]

2024-03-03 | GSE259376 | GEO

Comparative analysis of kidney organoid and adult human kidney single cell and single nucleus transcriptomes

Project description:We analyzed single cell transcriptomes over 80,000 cells isolated from 65 organoids differentiated from iPSCs and ESCs using two different protocols. We find that both protocols generate kidney organoids that contain a diverse range of kidney cells at differing ratios as well as non-renal cell types. We reconstructed lineage relationships during organoid differentiation through pseudotemporal ordering, and identified transcription factor networks associated with fate decisions. When comparing to adult human kidney, we reveal immaturity of all kidney organoid cell types. These results define impressive kidney organoid cell diversity, identify incomplete differentiation as a major roadblock for current directed differentiation protocols and provide a human adult kidney snRNA-seq dataset against which to benchmark future progress.

2018-10-13 | GSE118184 | GEO

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