Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Patient-iPSC-derived kidney organoids show functional validation of a ciliopathic renal phenotype

ABSTRACT: Purpose: A proof of concept study examining the disease modelling capabilities of patient iPSC derived kidney organoids. Methods: A proband was diagnosed by genome sequencing with compound heterozygous IFT140 mutations. A one-step reprogramming/gene-editing protocol of proband fibroblasts was used to derive both uncorrected patient and isogenic gene-corrected induced pluripotent stem cells (iPSC) which were differentiated to kidney organoids. Organoids were examined by immunofluorescence. Additionally, epithelial cells magnetically sorted from whole kidney organoids underwent transcriptional profiling and spheroid culture. Results: Differential expression analysis of organoid epithelial cell fractions demonstrated apicobasal polarity, cell-cell junction and dynein motor assembly downregulation in patient organoids. Defective ciliary morphology and spheroid culture were rescued in gene corrected organoids. Conclusions: This study validates patient iPSC-derived kidney organoids as a novel, faithful and patient-specific model to further the study of inherited renal disease in regenerated, human, in vitro tissue.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107230 | GEO | 2018/04/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

iPSC-derived type IV collagen α5-expressing kidney organoids model Alport syndrome

Project description:Alport syndrome (AS) is a hereditary glomerulonephritis caused by COL4A3, COL4A4 or COL4A5 gene mutations and characterized by abnormalities of glomerular basement membranes (GBMs). Due to a lack of curative treatments, the condition proceeds to end-stage renal disease even in adolescents. Hampering drug discovery is the absence of effective in vitro methods for testing the restoration of normal GBMs. Here, we aimed to develop kidney organoid models from AS patient iPSCs for this purpose. We established iPSC-derived collagen α5(IV)-expressing kidney organoids and confirmed that kidney organoids from COL4A5 mutation-corrected iPSCs restore collagen α5(IV) protein expression. Importantly, our model recapitulates the differences in collagen composition between iPSC-derived kidney organoids from mild and severe AS cases. Furthermore, we demonstrate that a chemical chaperone, 4-phenyl butyric acid, has the potential to correct GBM abnormalities in kidney organoids showing mild AS phenotypes. This iPSC-derived kidney organoid model will contribute to drug discovery for AS.

2023-07-06 | GSE236314 | GEO

RNA-seq of retinal organoids derived from RPGR patient-, control- and mutation-corrected-iPSC at different developmental stages

Project description:Retinitis pigmentosa (RP) is an irreversible and inherited retinopathy. RPGR mutations are the most common causes of this disease. It remains challenging to decipher the mechanism of RPGR mutation because of the lack of appropriate study models. The substitution of patient-specific diseased retina without ethical restrictions is desired and iPSC-derived 3D retina is the best choice. In our experiment, we generated iPSCs from one RP patient with 2-bp frameshift mutation in the exon14 of RPGR gene, which were differentiated into retinal organoids. Also we generated iPSCs from a normal control and differentiated those control-iPSCs into healthy retinal organoids. Samples of patient- and control-retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates for patient) were collected for RNA-seq. Corrected-iPSC were derived from CRISPR/Cas9-mediated gene correction. Then we collected the corrected-iPSC derived retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates) for RNA-seq. Through the RNA-seq data, we demonstrate that patient-specific iPSC-dervied 3D retinae can recapitulate disease progress of Retinitis Pigmentosa through presenting defects in photoreceptors' gene profile. CRISPR/Cas9-mediated gene correction can rescue photoreceptor gene profile. Those transcriptome are consistent with the phenotype and function.

2020-02-01 | E-MTAB-6490 | biostudies-arrayexpress

Transcriptional profiling of organoid glomeruli isolated from human kidney organoids modelling congenital nephrotic syndrome

Project description:To investigate the impact of various NPHS2 homozygous point mutations on podocyte biology in induced pluripotent stem cell (iPSC)-derived human kidney organoids, an iPSC allelic series was generated from a control fibroblast line and two iPSC lines were derived from patient blood samples (one homozygous R168H and one unaffected relative) iPSCs were differentiated into kidney organoids, organoids glomeruli were harvested and we performed gene expression profiling using data obtained from RNA-seq of 3 sets of 4 organoids for each genotype at D7+14 of our differentiation protocol (Takasato et al, Nature 2016)

2022-09-07 | GSE205647 | GEO

Lin28R192G mutation in Parkinsons's disease

Project description:mRNA-seq analyses for the differentially expressed genes (DEGs) between Parkinsons's disease patient (holding Lin28 R192G hetero mutation)-iPSC (Pt-iPSC) derived neural stem cell vs Lin28 R192G hetero mutation corrected-iPSC (Corrected Pt-iPSC) derived neural stem cell. To gain further molecular insight into the observed Lin28R192G mutation in Parkinsons's disease (PD) patient iPSC-derived neural stem cell (NSC) functions, we performed mRNA-sequencing (RNA-seq) analysis of the PD patient (holding Lin28 R192G hetero mutation)-iPSC (Pt-iPSC) derived NSC and Lin28 R192G hetero mutation corrected-iPSC (Corrected Pt-iPSC) derived NSC.

2019-08-20 | GSE135995 | GEO

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Project description:Single-cell RNA-seq of iPSC derived human kidney organoids. Single-nuclei RNA-seq data of COVID-19 patient autopsy kidney tissue. The current data was used to suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury as well as a pro-fibrotic environment which could explain acute kidney injury in COVID-19 patients and also long-term effects potentially leading to the development of chronic kidney disease.

2021-12-16 | GSE167747 | GEO

The immunogenicity of human kidney organoids

Project description:Safety issues of human iPSC-derived kidney organoids as a regenerative therapy need to be evaluated. Therefore, we studied the immunogenicity of human iPSC-derived kidney organoids. We subcutaneously implanted kidney organoids in immune-deficient IL2Ry-/-RAG2-/- mice for 1 month and hereafter performed adoptive transfer of healthy allogeneic human PBMC. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of kidney organoid cells and immune cell profiles. We investigated whether innate and adaptive immune cells invade kidney organoids, evoke an immune response, and influence the kidney organoid differentiation and functional capacity. Understanding the immunogenicity of kidney organoids will advance studies in the applicability of kidney organoids for regenerative medicine. Furthermore, it can serve as an in-vivo transplantation model to study solid organ transplantation.

2022-08-25 | GSE211803 | GEO

Proteomic analysis of induced pluripotent stem cell-derived kidney organoids

Project description:Kidney organoids were generated from a control iPSC line using a previously published protocol (https://doi.org/10.1038/nprot.2016.098). Organoids were collected at three timepoints during the protocol (day 14, 18 and 25) and prepared for proteomic analyses. The focus of the study was to define the proteomic composition of kidney organoids during differentiation with a particular emphasis on the extracellular matrix and its comparison to in vivo systems. Following a ample fractionation and matrix enrichment strategy, samples were prepared for high resolution label-free tandem mass spectrometry to define the proteomic composition of human kidney organoids.

2021-10-13 | PXD025838 | Pride

Kidney organoid reproducibility across multiple human iPSC lines and diminished off target cells after transplantation revealed by single cell transcriptomics

Project description:Human iPSC-derived kidney organoids have the potential to revolutionize discovery, but assessing their consistency and reproducibility across iPSC lines, and reducing the generation of off-target cells remain an open challenge. Here, we used single cell RNA-Seq (scRNA-Seq) to profile 450,118 cells to show that organoid composition and development are comparable to human fetal and adult kidneys. Although cell classes were largely reproducible across iPSC lines, time points, protocols, and replicates, cell proportions were variable between different iPSC lines. Off-target cell proportions were the most variable. Prolonged in vitro culture did not alter cell types, but organoid transplantation under the mouse kidney capsule diminished off-target cells. Our work shows how scRNA-seq can help score organoids for reproducibility, faithfulness and quality, that kidney organoids derived from different iPSC lines are comparable surrogates for human kidney, and that transplantation enhances their formation by diminishing off-target cells.

2019-11-04 | GSE136314 | GEO

Patient-iPSC-derived kidney organoids show functional validation of a ciliopathic renal phenotype

Project description:Patient-iPSC-derived kidney organoids show functional validation of a ciliopathic renal phenotype

| PRJNA419394 | ENA

Kidney organoids are capable of forming Wilms-like tumors, but not teratomas

Project description:To study safety and stability of kidney organoids, we studied the presence of residual iPSC in the kidney organoids. We also analyzed their potential for malignant transformation in a teratoma assay and following long-term subcutaneous implantation in an immune deficient mouse model.

2021-01-22 | GSE165266 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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