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Kidney organoids derived from human induced pluripotent stem cells (iPSC)

ABSTRACT: kidney organoids derived from human induced pluripotent stem cells (iPSC)

PROVIDER: PRJNA722961 | ENA |

REPOSITORIES: ENA

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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

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

Project description: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.

2018-04-26 | GSE107230 | GEO

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

scRNAseq of human iPSC-derived kidney organoids transplanted in the coelomic cavity of chicken embryos compared to untransplanted controls

Project description:Human induced pluripotent stem cell-derived kidney organoids have potential for disease modelling and regenerative medicine purposes. However, they lack a functional vasculature and remain immature in in vitro culture. Here, we transplanted kidney organoids at day 7+12 of differentiation in the coelomic cavity of chicken embryos and then compared them to their respective untransplanted controls at d7+13 and d7+20 using scRNAseq and imaging modalities. We demonstrate vascularization and enhanced maturation of transplanted kidney organoids.

2022-08-05 | E-MTAB-11429 | biostudies-arrayexpress

The nephrotxin Puromycin aminonucleoside induces injury in kidney organoids differentiated from human urine SIX2-positive stem cell derived induced pluripotent stem cells.

Project description:Kidney diseases including acute kidney injury (AKI) and chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD), are a worldwide health burden. Organ trans-plantation or kidney dialysis are the only effective available therapeutic tools. Therefore, in vitro models of kidney diseases and the development of prospective therapeutic means are highly demanded. Within the kidney, the glomeruli are involved in blood filtration and waste excre-tion, and are easily affected by changing cellular conditions. Puromycin aminonucleoside (PAN) is a nephrotoxin, which can be harnessed for imitating acute glomerular damage and modelling of glomerular disease. For this reason, we generated kidney organoids from three iPSC lines and treated these with PAN in order to induce kidney injury. Morphological observations re-vealed disruption of glomerular and tubular structures within the kidney organoids upon PAN treatment, which were confirmed by transcriptome analyses. Subsequent analyses revealed an upregulation of immune response as well as inflammatory and cell death-related processes. We concluded that treatment of iPSC-derived kidney organoids with PAN induces kidney injury mediated an intertwined network of inflammation, cytoskeletal re-arrangement, DNA damage, apoptosis and cell death. Furthermore, urine stem cell-derived kidney organoids can be used for modelling of kidney-associated diseases and drug discovery.

2022-03-04 | GSE186823 | GEO

kidney organoids derived from human induced pluripotent stem cells (iPSC)

Project description:iPSCs were maintained on Geltrex coated flat culture dish in E8 media according to manufacturer’s guidelines. Colonies were manually harvested at 60-80% confluence. Cells were then collected and dissociated into single cells using EDTA. Cells were put on to ultra low attachment 24 well or 96 well plate to allow them to form aggregated in suspension with ROCK inhibitor. Cell aggregates 191were cultured in E8 medium with daily medium change for 6-7 days. Control iPSC-A (iPSC-aggregates) were plated on a Geltrex in 96 well plate or 8 well culture chamber. And then aggregates were treated E8 medium with daily medium change for 12-14 days.

2021-04-20 | GSE172319 | GEO

Vascular organoids differentiation from human induced pluripotent stem cells (iPSC)

Project description:Vascular organoids differentiation from human induced pluripotent stem cells (iPSC)

| PRJNA428378 | ENA

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

Single cell RNA-seq of iPSC-derived Kidney Organoids treated with TGF-Beta 1 and GSK343 compared with vehicle treated control

Project description:This study used scRNA-seq to characterise the transcriptome in 26 day-old iPSC-derived kidney organoids, treated with TGFB1, the EzH2 inhibitor GSK343, a combination of both or a vehicle control for 48 hours (days 24-26) before harvesting. 2 organoids per condition were pooled and dissociated using a cold-active protease. Nuclei were extracted and profiled using the 10X Genomics Single-cell 3' V3 kits. Libraries were sequenced using paired-end reads on an Illumina NextSeq 500. Initial processing was performed using CellRanger v3.1.0 (10X Genomics).

2023-04-30 | E-MTAB-11138 | biostudies-arrayexpress

Single cell ATAC-seq of iPSC-derived Kidney Organoids treated with TGF-Beta 1 and GSK343 compared with vehicle treated control

Project description:This study used snATAC-seq to profile Chromatin accessibility in 26 day-old iPSC-derived kidney organoids, treated with TGFB1, the EzH2 inhibitor GSK343, a combination of both or a vehicle control for 48 hours (days 24-26) before harvesting. 2 organoids per condition were pooled and dissociated using a cold-active protease. Nuclei were extracted and profiled using the 10X Genomics Single-cell ATAC reagent kit v1.1. Libraries were sequenced using paired-end reads on an Illumina NovaSeq 6000. Initial processing was performed using CellRanger ATAC v1.2.0 (10X Genomics).

2023-04-30 | E-MTAB-11139 | biostudies-arrayexpress

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