Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB18273 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR572095_1.fastq.gz | Fastqsanger.gz | |||
| DRR572095_2.fastq.gz | Fastqsanger.gz | |||
| DRR572096_1.fastq.gz | Fastqsanger.gz | |||
| DRR572096_2.fastq.gz | Fastqsanger.gz | |||
| DRR572097_1.fastq.gz | Fastqsanger.gz |
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Project description:Kidney organoids can be generated from commercially available human induced pluripotent stem cells (iPSC). They are amenable for genetic manipulation and useful for modelling development and early-onset genetic diseases. However, iPSC-derived kidney organoids lack longevity to model chronic stressors associated with chronic kidney disease. Adult epithelial kidney organoids (tubuloids) derived from nephrectomies or from renal cells suspended in urine can be passaged, expanded and cryopreserved, offering avenues to model epithelial injury and repair over longer timeframes. However, patient-derived organoids face regulatory barriers in their utilization. To leverage the benefits of both models, we establish a new protocol to generate tubuloids from iPSC-derived kidney organoids (iTubuloids). Kidney organoids were produced from iPSCs by directed differentiation then dissociated and cultured under adult organoid culture conditions. Epithelial organoids formed in less than 3 days from three distinct iPSC lines, each of which have been passaged > 12 times. Comparative analysis of gene expression profiles with RNA sequencing suggested that adult-derived tubuloids better represented the collecting duct, and iTubuloids showed increased expression of proximal and some distal markers. However, expression of proximal tubule markers was higher in iPSC-derived kidney organoids than any tubuloid model. We then evaluated the capacity of iTubuloids to model repetitive kidney injury and found exacerbation of the response and signs of failed repair as the injured progressed. Our study affirms capacity to extend the lifespan of epithelial cell types from short-lived iPSC-derived kidney organoids and reveal a need to optimise nephron cell identities in the tubuloid culture.
2025-04-30 | GSE252055 | GEO
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
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
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
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 | GSE259376 | GEO
Project description:Acquired drug resistance is the major therapeutic obstacle to maintenance treatment of advanced-stage non-small cell lung cancer. Lung adenocarcinoma (ADC) harboring driver mutations also showed poor response to immune checkpoint inhibitors (ICIs). Underlying mechanisms of how drug insensitivity evolves remain unclear. Here we explored the intratumoral heterogeneity of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (ALK)-rearranged lung ADC organoids using single-cell RNA-sequencing (scRNA-seq) transcriptomic analysis. IL-17 signaling pathway was found highly induced in a subpopulation of pre-existing ALK-TKI-resistant cells. These drug-tolerant persister (DTP) cells, also found to have high surface intracellular adhesion molecule 1 (ICAM-1) expression level, were more resistant towards ALK-TKI and expressed a higher level of cancer-stem cell transcriptional factors. Moreover, tumor cells with high ICAM-1 expression were found spatially correlated with RORɣt+ Th17 infiltration in ALK-rearranged NSCLC resected tumor tissues. In conclusion, our data revealed marked intratumoral heterogeneity in ALK-rearranged tumor, and pre-existing DTP cells may contribute to the development of drug insensitivity in ALK-rearranged lung ADC.
2023-08-09 | GSE223779 | GEO
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
Project description:Human iPSC-derived renal collecting duct organoids model cystogenesis in ADPKD
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Project description:Human iPSC-derived renal collecting duct organoids model cystogenesis in ADPKD
| PRJNA891209 | ENA