Homo sapiens
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ABSTRACT:
PROVIDER: PRJDB14555 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human iPSC-derived renal collecting duct organoids model cystogenesis in ADPKD
| PRJDB14510 | ENA
Project description:Human iPSC-derived renal collecting duct organoids model cystogenesis in ADPKD
| PRJNA891209 | ENA
Project description:Here, establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to collecting ducts, we succeeded in advancing the developmental stage of collecting duct organoids and showed that all collecting duct organoids derived from PKD1-/- hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis.
2023-11-30 | GSE215875 | GEO
Project description:Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal genetic disease, with most patients carrying mutations in PKD1. The main feature is the formation of bilateral renal cysts, leading to end stage renal failure in a significant proportion of those affected. Despite recent advances made in understanding ADPKD, there are currently no effective curative therapies. The emergence of human induced pluripotent stem cell (hiPSC)-derived kidney disease models has led to renewed hope that more physiological systems will allow for the development of novel treatments. hiPSC-derived organoid models have been used to recapitulate ADPKD, however they present numerous limitations which remain to be addressed. In the present study, we report an efficient method for generating organoids containing a network of polarised and ciliated epithelial tubules. PKD1 null (PKD1-/-) organoids spontaneously develop dilated tubules, recapitulating early ADPKD cystogenesis. Furthermore, PKD1-/- tubules present primary cilia defects when dilated. Our model could therefore serve as a valuable tool to study early ADPKD cystogenesis and to develop novel therapies.
2025-01-15 | GSE286070 | GEO
Project description:Current renal organoid models, typically derived from pluripotent stem cells, recapitulate aspects of kidney development but are constrained by cellular immaturity and off-target populations. Here, we establish an expandable renal organoid system from adult patient kidney tissues, comprising proliferative epithelial progenitors and differentiated proximal tubule and collecting duct lineages. Leveraging this system, we generated “petal-like” polycystic organoids from PKD1 or PKD2 mutant tissues that faithfully mimic the morphological and functional hallmarks of ADPKD. Mechanistic investigation revealed that RHO signaling may serve as a candidate component of the cilia-dependent cyst activation (CDCA) mechanism that drives cystogenesis. Subsequent drug screening identified RHO GTPase inhibitors as selective suppressors of cyst growth across multiple organoid lines. This patient tissue-derived organoid platform offers a physiologically relevant and robust model for investigating cytogenic mechanisms and enabling precision therapeutic discovery and drug screen in polycystic kidney disease.
2025-05-15 | GSE296369 | GEO
Project description:Current renal organoid models, typically derived from pluripotent stem cells, recapitulate aspects of kidney development but are constrained by cellular immaturity and off-target populations. Here, we establish an expandable renal organoid system from adult patient kidney tissues, comprising proliferative epithelial progenitors and differentiated proximal tubule and collecting duct lineages. Leveraging this system, we generated “petal-like” polycystic organoids from PKD1 or PKD2 mutant tissues that faithfully mimic the morphological and functional hallmarks of ADPKD. Mechanistic investigation revealed that RHO signaling may serve as a candidate component of the cilia-dependent cyst activation (CDCA) mechanism that drives cystogenesis. Subsequent drug screening identified RHO GTPase inhibitors as selective suppressors of cyst growth across multiple organoid lines. This patient tissue-derived organoid platform offers a physiologically relevant and robust model for investigating cytogenic mechanisms and enabling precision therapeutic discovery and drug screen in polycystic kidney disease.
2025-05-15 | GSE295223 | GEO
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: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
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.
2023-08-28 | GSE228971 | GEO