Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Kidney micro-organoids generated in suspension culture

ABSTRACT: Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scale-up production of kidney cell types in vitro. We describe here a modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells. Each micro-organoid contains 6-10 nephrons surrounded by endothelial and stromal populations. Single cell transcriptional profiling confirmed the presence and transcriptional equivalence of all anticipated renal cell types consistent with a previous organoid culture method. Ligand-receptor mapping identified TGFβ signalling between stromal and epithelial cell types as likely to result in fibrotic changes observed with long-term culture. The addition of an ALK4 inhibitor suppressed stromal expansion, maintaining epithelial morphology and improving maturation. This suspension culture micro-organoid methodology resulted in a 3-4-fold increase in final cell yield compared to static culture, thereby representing an economical approach to the production of kidney cells for various biological applications.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117211 | GEO | 2019/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Kidney micro-organoids generated in suspension culture

Project description:Kidney micro-organoids generated in suspension culture

| PRJNA481467 | ENA

Kidney Organoids treated with TNFa at 5 ng/mL and 50ng/mL for 24h and 48h

Project description:This dataset serves as comparison for PXD029718 using a different organoid differentiation protocol – as requested by reviewers. Kidney organoids are a promising model to study kidney disease, but use is constrained by limited knowledge of their functional protein expression profile. We aimed to define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increased deposition of extracellular matrix but decreased expression of glomerular proteins. Single cell transcriptome integration revealed that most proteome changes localized to podocytes, tubular and stromal cells. TNFα-treatment of organoids effected 320 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 320 proteins was significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression was increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing to human data, we provide crucial evidence of functional relevance of the kidney organoid model to human kidney disease.

2023-05-12 | PXD040812 | Pride

An Organoid Biobank for Childhood Kidney Cancers that Captures Disease and Tissue Heterogeneity

Project description:Kidney tumours are among the most common solid tumours in children, comprising several distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. The malignant rhabdoid tumour organoids represent the first organoid model for tumours of non-epithelial origin. The tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug vulnerabilities. We further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like. Our organoid biobank captures the cellular heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterized models for basic cancer research, drug-screening, and personalized medicine.

2019-09-18 | GSE137544 | GEO

Fine tuning of epithelial taste bud organoid to promote functional recapitulation of taste reactivity

Project description:Taste stem/progenitor cells from the mouse posterior tongue have been recently used to generate taste bud organoids. However, the inaccessible location of the taste receptor cells is observed in conventional organoids. Here, we established a suspension culture method for fine tuning of taste bud organoid by apicobasal polarity alteration to form the accessible localization of taste receptor cells in organoid. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed comparable differentiation and renewal rates to those of taste buds in vivo and exhibited functional taste receptor cells and cycling progenitor cells. Accessible taste receptor cells on the outer region of taste bud organoids enabled the direct application of calcium imaging for evaluating the taste response. Moreover, suspension-cultured organoids could be genetically altered using gene editing methods. Suspension-cultured taste bud organoid harmoniously integrated with the recipient lingual epithelium; maintained the taste receptor cells and gustatory innervation capacity. Thus, we propose that suspension-cultured organoids may provide efficient model for taste research including taste bud development, regeneration and transplantation

2021-12-25 | GSE191169 | GEO

Kidney organoids gene expression profile

Project description:Exploring gene expression profile in kidney organoids cultured by static and suspension culture system in different time point

2022-01-01 | GSE164648 | 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

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

High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays

Project description:Stem-cell-derived epithelial organoids are routinely used for the biological and biomedical modelling of tissues. However, the complexity, lack of standardization and quality control of stem cell culture in solid extracellular matrices hampers the routine use of the organoids at industrial scale. Here, we report the fabrication of microengineered cell-culture devices and scalable and automated methods for the suspension culture and real-time analysis of thousands of individual gastrointestinal organoids trapped in microcavity arrays within a polymer-hydrogel substrate. The absence of a solid matrix significantly reduces organoid heterogeneity, as we show for mouse and human gastrointestinal organoids. We used the devices to screen for anticancer drug candidates with patient-derived colorectal cancer organoids, and high-content image-based phenotypic analyses to reveal insights into drug-action mechanisms. The scalable organoid-culture technology should facilitate the use of organoids in drug development and diagnostics.

2020-04-10 | GSE148347 | GEO

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

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

2023-08-28 | GSE228971 | GEO