Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human iPSC-derived renal organoids engineered to report oxidative stress can predict drug-induced nephrotoxicity

ABSTRACT: The purpose of this study was primarily to find a reporter of nephrotoxicity that could be engineered into human pluripotent stem cells, and then to assess the performance of that reporter using a panel of test compounds. We treated renal organoids with two different concentrations of Gentamicin, 1mg/ml (low concentration) and 4 mg/ml (high concentration), and used RNA-seq to compare the expression profile of these groups to the expression profile of untreated control group. In our RNA-seq analyses, the profile of the 4 mg/ml gentamicin-treated samples was strikingly different from that of the control group.There were no genes expressed significantly differently between the control and the 1 mg/ml gentamicin-treated samples. classical markers of nephrotoxicity were either not up-regulated in response to injury (CLU) or were down-regulated (NGAL) in response to the known nephrotoxicant gentamicin. Among the transcripts showing increased expression was KIM-1 (log fold-change: 1.67; FDR-corrected p = 0.03), a biomarker commonly associated with renal tubular necrosis. Expression of the oxidative stress marker HMOX1 was also highly increased (log fold-change: 6.55; FDR-corrected p = 0.00015). Based on the intersection of HMOX1 in several different toxicity pathways as well as its greater level of up-regulation, we identified HMOX1 as a potentially promising reporter for one large class of nephrotoxicants; those in which the OS pathway is activated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE195642 | GEO | 2022/01/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from the kidney of Sprague-Dawley rats given colistin methanesulfonate sodium

Project description:To investigate the mechanism of nephrotoxicity, colistin methanesulfonate sodium (CMS; 25 or 50 mg/kg) was administered via intraperitoneal injection to Sprague–Dawley rats daily over 7 d. Affymetrix GeneChip microarrays indicated 894 differentially expressed genes in groups treated with CMS (ANOVA, FDR < 0.05, fold change ≥ 1.3).

2018-10-26 | GSE121792 | GEO

Transcription profiling of S. cerevisiae treated with gentamicin

Project description:Gentamicin is a highly efficacious antibiotic against gram-negative bacteria. However, its usefulness in treating infection is compromised by its poorly understood renal toxicity. This toxic effect is seen in a variety of organisms. While the yeast Saccharomyces cerevisiae is relatively insensitive to gentamicin, mutations in any one of 20 or so genes causes a dramatic increase in sensitivity. Many of these genes encode proteins important for translation termination or specific protein trafficking complexes. Here, we demonstrate by microarray analysis that gentamicin treatment leads to dramatic decreases in genes under the control of the MADS box protein Mcm1, including genes encoding products involved in mating, nitrogen utilization, and ribosome biogenesis. Furthermore, microarray analysis also demonstrates an increase in a Rlm1-dependent set of genes involved in maintaining the structure of the cell wall that are also induced by the antifungal agents caspofungin and calcofluor white. Subsequent inspection of the physical and genetic interactions of the remaining gentamicin sensitive mutants revealed a network centered around chitin synthase and the Arf Pathway. Furthermore, conditional arf1 mutants are hypersensitive to gentamicin even under permissive conditions. These results suggest that gentamicin may act as a cell wall stress, possibly by disrupting Arf-dependent trafficking of proteins involved in forming the cell wall. Experiment Overall Design: The yeast strain 4073 was grown to mid-log with and without gentamicin (500 mg/ml) (n=4 for each condition). Yeast cells were pelleted and snap frozen. Total RNA was isolated using the Epicentre Masterpure Yeast RNA Purification kit. RNA samples were brought to the Indiana University Center for Medical Genomics who performed the microarray analysis using Affymetrix GeneChip Scanner 3000 and the Affymetrix Yeast arrays.

2008-06-15 | E-GEOD-7188 | biostudies-arrayexpress

Effects of gentamycin on gene expression of kidney in SD rats

Project description:To investigate the gene expression profile of genamycin induced nephrotoxicity in a time-series aspect, SD rats were administrated once daily with saline, genamycin 80 mgkg for 28 consecutive days by intramuscular injection folled by 28 days recovery. Kidney samples were collected for microarray analysis and histological examination. There were 4360 and 4323 regulated genes for females and males, respectively, however, the overlapping expression genes coregluated at each time point were few, with 2 for females and 12 for males. By Principle Component Analysis and Hierarchical Cluster, the gene expression patterns were apparently associated with the disease stage of the nephrotoxicity,while GO Annotation showed the biological processes were specific to each course of this nephrotoxicity.Our studymapped the different gene expression patterns at the initiation, development and recovery stage of gentamycin-induced nephrotoxicity Gene expression in kidney from SD rats administrated once daily with saline or 80 mg/kg genamycin by intramuscular injection for 28 consecutive days follwed by 28 days recovery were measured using Aglient Rat Whole Genome 4*44 k array

2013-09-13 | E-GEOD-50804 | biostudies-arrayexpress

C. elegans : Control vs. Chlorpyrifos (0.5mg/ml) + Diazinon (1 mg/ml) treatment

Project description:Transcriptional profile of C. elegans comparing control vs. nematodes treated with 0.5 mg/ml of Chlorpyrifos and 1mg/ml of Diazinon (DZN) at 16°C. Toxicant was added to agar and nematode culture on petri dishes for 72h before harvesting.

2010-07-22 | GSE16698 | GEO

Caenorhabditis elegans

Project description:C. elegans : Control vs. Chlorpyrifos (0.5mg/ml) + Diazinon (1 mg/ml) treatment

| PRJNA122797 | ENA

Viral Effect on Metabolism (part I)

Project description:Small airway epithelial cell (SAEC) (Lonza Walkersville, Inc., MD) were grown according to the manufacturer's instructions in growth medium (SAGM) containing 0.03 mg/ml bovine pituitary extract (BPE), 0.5 µg/ml hydrocortisone, 0.5 ng/ml hEGF, 0.5 µg/ml epinephrine, 10 µg/ml transferrin, 5 µg/ml insulin, 0.1 ng/ml retinoic acid, 6.5ng/ml triiodothyronine, 50 µg/ml gentamicin and 50ng/ml Amphotericin-B, and 0.5 mg/ml bovine serum albumin (BSA, fatty acid free). When SAE grew to around 80 to 90% confluence, the cells were put into basal medium not supplemented with growth factors 3hours. Then the cell monolayers were infected with naïve hMPV at multiplicity of infection (MOI) of 3 to certain time. The supernatant was saved and cells were harvested and stored exactly according to the protocol provided by University of Michigan Metabolomics Core Facility for metabolomics analysis. 50mM ammonium acetate in water was used for rinse buffer.

2014-10-24 | ST000278 | MetabolomicsWorkbench

Viral Effect on Metabolism (part II)

2015-02-05 | ST000279 | MetabolomicsWorkbench

Gene expression signature in Lactococcus lactis after ethanol, butanol or hexanol exposure

Project description:Reference samples: Strain MG1363 was grown balanced in SAL medium supplemented with 1% glucose. Stressed samples: Strain MG1363 was exposed to either ethanol (55 mg/ml), butanol (10 ml/mg) or hexanol (2 mg/ml) in GSAL medium after balanced growth

2016-11-04 | GSE89508 | GEO

Transcription profiling of Listeria monocytogenes after infection into murine macrophages

Project description:P388D1 murine macrophages were cultured in 85 mm tissue culture plates to about semi confluency. L. monocytogenes serotypes (1/2a EGD-e, 4a L99, 4b CLIP80459 and 4b F2365) were infected to the P388D1 cell monolayer at a MOI of 100 per eukaryotic cell. Infection was carried for 45 min and followed by addition of fresh medium containing 20 M-5g/ml gentamicin. The medium of the plates (containing 20 M-5g/ml gentamicin) infected with L. monocytogenes serotypes were replaced after 2 h post infection with fresh medium containing 50 M-5g/ml gentamicin. At each step the plates were washed extensively with 1x PBS. Incubation of the bacterial tissue culture plates was carried out in a humidified incubator for up to 4 h post infection.

2010-11-25 | E-MEXP-1947 | biostudies-arrayexpress

RNA-seq of human gut Bacteroides xylanisolvens and Bacteroides ovatus isolates grown on mucin O-linked glycans compared to glucose

Project description:Purpose: Examining the transcriptome of human gut bacteria (Bacteroides xylanisolvens/Bacteroides ovatus) that grow on mucin O-linked glycans as a sole carbon source Methods: Strains were grown on 10 mg/ml mucin O-linked glycans (MOG) or 5 mg/ml glucose as a sole carbon source in vitro. Fold change was calculated as MOG over glucose. Once cells reached an optical density corresponding to mid-log phase growth, RNA was isolated and rRNA depleted. Samples were multiplexed for sequencing on the Illumina HiSeq platform at the University of Michigan Sequencing Core. Data was analyzed using Arraystar software (DNASTAR, Inc.) Genes with significant up- or down-regulation were determined by the following criteria: genes with an average fold-change >10-fold and biological replicates with a normalized expression level >1% of the overall average RPKM expression level. Results: We identified genes activated in response to mucin O-linked glycans from Bacteroides xylanisolvens/Bacteroides ovatus strains

2020-12-01 | GSE155869 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data