Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Niche-inspired tubuloid differentiation enables modeling of the distal nephron in health and disease

ABSTRACT: Tubuloid culture allows long-term expansion of primary human renal epithelium. However, the progenitor state in expanding tubuloids comes at expense of differentiation, which limits application. To improve differentiation, we developed niche-inspired culture conditions. A single cell atlas revealed that differentiation predominantly generated ascending limb of Henle and principal cells. Using differentiated tubuloids, we subsequently modeled lithium nephropathy in vitro, and performed single-cell RNA sequencing to look at the transcriptional effects caused by lithium. We found that lithium suppresses electrolyte and solute transporters in multiple cell types and induces a progenitor state in kidney tubuloids.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206538 | GEO | 2022/10/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

GDNF drives rapid tubule morphogenesis in novel 3D in vitro model for ADPKD [GDNF RNAseq]

Project description:We report a significant change in epithelial differentiation pathways and principal cell specific transcription factors in tubuloids with a GDNF pulse, when compared to control tubuloid cultures.

2020-06-08 | GSE151949 | GEO

Single-cell RNA sequencing of differentiated human iPSC organoid-derived kidney tubuloids (iPSCod tubuloids)

Project description:Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Here, we apply recently developed tubuloid protocols to purify and propagate kidney epithelium from d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting ‘iPSC organoid-derived (iPSCod)’ tubuloids can be exponentially expanded for at least 2.5 months, while retaining expression of important tubular transporters and segment-specific markers. This approach allows for selective propagation of the mature tubular epithelium, as immature cells, stroma, and undesirable off-target cells rapidly disappeared. iPSCod tubuloids provide easy apical access, which enabled functional evaluation and demonstration of essential secretion and electrolyte reabsorption processes. In conclusion, iPSCod tubuloids provide a different, complementary human kidney model that unlocks opportunities for functional characterization, disease modeling, and regenerative nephrology.

2026-04-30 | GSE303210 | GEO

Niche-inspired tubuloid differentiation enables modeling of the distal nephron in health and disease

Project description:Niche-inspired tubuloid differentiation enables modeling of the distal nephron in health and disease

| PRJNA851357 | ENA

Comparative analysis of human kidney organoid and tubuloid models

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

Human Kidney Tubuloids Model of Repeated Cisplatin-induced Cellular Senescence and Fibrosis for Drug Screening

Project description:In the pursuit of pathophysiological models for assessing renal drug response, the development of kidney organoids derived from human pluripotent stem cells represents a significant step forward. However, recapitulating aging/senescence-associated pathophysiology remains challenging. Here, we present an innovative approach to generate epithelial-like structures known as “tubuloid” using primary human renal proximal tubular epithelial cells (hRPTECs) cultured from human resected kidneys, as a refined alternative. We evaluated the efficacy of tubuloids using cisplatin treatment. Tubuloids showed highly differentiated structures. Exposure to cisplatin increased γH2AX, Kidney Injury Molecule-1 (KIM-1) and Cleaved Caspase-3, markers for DNA damage response, epithelial damage and apoptosis respectively. Repeated cisplatin administration resulted in upregulation of the senescence markers. Additionally, increased secretion of inflammatory cytokines, indicating the induction of a senescence-associated secretory phenotype (SASP) were induced Supernatant collected from cisplatin-treated tubuloids induced myofibroblast activation, indicating the onset of renal fibrosis. We successfully established a tubuloid-based model of cisplatin-induced kidney injury using hRPTECs. Tubuloids can replicate cellular senescence, SASP, and fibrosis, which can recapitulate the phenotypes of chronic kidney disease (CKD). Furthermore, tubuloids provide a novel platform for studying the response of renal epithelial cells to toxins and therapeutics and offer innovative strategy for drug screening in a human-based fashion. In this study, we also performed bulk RNA sequencing on the tubuloids generated using established protocol to verify their cellular composition.

2026-02-25 | GSE302756 | GEO

Renal cell-derived extracellular vesicles as a modulator of tubuloid functional maturation

Project description:Tubuloids are adult stem cell-based kidney organoids with promising application in kidney disease modelling and drug screening. However, tubuloids still present limited transepithelial transport capacity, which is essential for the kidney’s function. The extracellular vesicles (EVs) are cell-derived vesicular structures known to regulate several cellular processes, including development and maturation. This study explores the potential of EVs derived from renal cells to support tubuloid functional maturation by increasing the levels of organic anion transport 1 (OAT1), a protein involved in renal waste handling.

2022-08-12 | PXD027142 | Pride

Project description:Optimizing Extraction Methods for Isolating Proximal Tubuloids through Enhanced Tubuloid Differentiation in Organoids

| PRJNA1153012 | ENA

The combination of valproic acid and lithium prevents hematopoietic stem/progenitor cell differentiation.

Project description:Expression profiles of 7-day cultured HSPCs in the presence or absence of valproic acid and/or lithium. Two small molecules, valproic acid (VPA) and lithium (Li), were tested to inhibit differentiation of hematopoietic stem/progenitor (HSPC) cells in culture. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients and enhanced in vivo repopulating potential. Furthermore, VPA and Li synergistically preserved expression of stem cell-related genes and repressed genes involved in differentiation. Target genes were collectively co-regulated during normal hematopoietic differentiation. Additionally, transcription factor networks were identified as possible primary regulators. Our results demonstrate that the combination of VPA and Li potently prevents differentiation at the biological and the molecular level, and provide evidence to suggest that combinatorial screening of chemical compounds may uncover possible additive/synergistic effects to modulate stem cell fate decisions. These data consist of total mRNA obtained from hematopoietic cells cultured for 7 days in the presence or absence of valproic acid and/or lithium. All samples were analyzed in independent biological triplicates.

2011-12-15 | E-GEOD-34088 | biostudies-arrayexpress

Expression profiles of 7-day cultured HSPCs in the presence or absence of valproic acid and/or lithium

Project description:Two small molecules, valproic acid (VPA) and lithium (Li), were tested to inhibit differentiation of hematopoietic stem/progenitor (HSPC) cells in culture. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients and enhanced in vivo repopulating potential. Furthermore, VPA and Li synergistically preserved expression of stem cell-related genes and repressed genes involved in differentiation. Target genes were collectively co-regulated during normal hematopoietic differentiation. Additionally, transcription factor networks were identified as possible primary regulators. Our results demonstrate that the combination of VPA and Li potently prevents differentiation at the biological and the molecular level, and provide evidence to suggest that combinatorial screening of chemical compounds may uncover possible additive/synergistic effects to modulate stem cell fate decisions. These data consist of total mRNA obtained from hematopoietic cells cultured for 7 days in the presence or absence of valproic acid and/or lithium. All samples were analyzed in independent biological triplicates.

2012-01-24 | E-GEOD-35291 | biostudies-arrayexpress

mRNA profiles of four developmentally related hematopoietic cell types (LSK, L-S-K+, Gr1+ and Ter119+) isolated from the BM of B6 and D2 mice

Project description:The combination of valproic acid and lithium delays hematopoietic stem\progenitor differentiation

2012-01-25 | GSE35292 | GEO