Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Directed differentiation to nephron progenitor cells [RNA Seq 1]

ABSTRACT: Metabolic pathways driving differentiation into nephron progenitor cells (NPCs) and renal organoids from the pluripotency stage remain poorly understood. In this study, we systematically performed comprehensive metabolite and transcriptome profiling of human pluripotent stem cells (hPSCs) during differentiation into NPCs and further into multicellular organoids. We found activation of distinct metabolic pathways during early-stage progression from hPSCs to NPCs; however, later-stage differentiation from NPCs to organoids, and the intervening developmental stages between them, largely shared similar metabolic profiles. Among the pathways changing in early differentiation, the alanine-aspartate-glutamate and glutamine pathways were found to be significantly altered by both an enrichment and by pathway impact analysis. Moreover, hPSCs survived glutamine deprivation during in vitro differentiation, and NPCs were successfully generated both in the absence and presence of glutamine and glutamate. Surprisingly, glutamine deprivation resulted in enhanced maturation, by accelerating PAX8 expression, and enriching for podocytes as detected through single cell RNA-Seq analysis. Taken together, these findings highlight a critical regulatory role of glutamine metabolism in the derivation of nephron progenitor cells and renal organoids and identify a controlling metabolic pathway of early renal differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128937 | GEO | 2022/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Directed differentiation to nephron progenitor cells in the presence and absence of glutamine [RNA Seq 2]

Project description:Metabolic pathways driving differentiation into nephron progenitor cells (NPCs) and renal organoids from the pluripotency stage remain poorly understood. In this study, we systematically performed comprehensive metabolite and transcriptome profiling of human pluripotent stem cells (hPSCs) during differentiation into NPCs and further into multicellular organoids. We found activation of distinct metabolic pathways during early-stage progression from hPSCs to NPCs; however, later-stage differentiation from NPCs to organoids, and the intervening developmental stages between them, largely shared similar metabolic profiles. Among the pathways changing in early differentiation, the alanine-aspartate-glutamate and glutamine pathways were found to be significantly altered by both an enrichment and by pathway impact analysis. Moreover, hPSCs survived glutamine deprivation during in vitro differentiation, and NPCs were successfully generated both in the absence and presence of glutamine and glutamate. Surprisingly, glutamine deprivation resulted in enhanced maturation, by accelerating PAX8 expression, and enriching for podocytes as detected through single cell RNA-Seq analysis. Taken together, these findings highlight a critical regulatory role of glutamine metabolism in the derivation of nephron progenitor cells and renal organoids and identify a controlling metabolic pathway of early renal differentiation.

2022-06-01 | GSE128938 | GEO

Glutamine deprivation enhances directed differentiation of renal organoids

Project description:Glutamine deprivation enhances directed differentiation of renal organoids

| PRJNA529412 | ENA

Modeling kidney development, disease, and plasticity with clonal expandable nephron progenitor cells and nephron organoids

Project description:Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The synthetic niche reprograms differentiated nephron cells into NPC state, recapitulating the plasticity of developing nephron in vivo. Scalability and ease of genome-editing in the cultured NPCs allow for genome-wide CRISPR screening, identi-fying novel genes associated with kidney development and disease. A rapid, efficient, and scala-ble organoid model for polycystic kidney disease was derived directly from genome-edited NPCs, and validated in drug screen. These technological platforms have broad applications to kidney development, disease, plasticity, and regeneration.

2024-03-14 | GSE251862 | GEO

A modular differentiation system maps multiple human kidney lineages from pluripotent stem cells [RNA-Seq]

Project description:Recent studies using human pluripotent stem cells (hPSCs) have developed protocols to induce kidney-lineage cells and reconstruct kidney organoids. However, the separate generation of metanephric nephron progenitors (NPs), mesonephric NPs and ureteric bud (UB) cells, which constitute embryonic kidneys, in in vitro differentiation culture systems has not been fully investigated. Here we created a culture system in which these mesoderm-like cell types as well as paraxial and lateral plate mesoderm-like cells were separately generated from hPSCs. We succeeded in recapitulating nephrogenic niches from separately induced metanephric NP-like and UB-like cells, which were subsequently differentiated into glomeruli, renal tubules and collecting ducts in vitro and further vascularized in vivo. Our selective differentiation protocols should contribute to understanding the mechanisms underlying human kidney development and diseases and also supply cell sources for regenerative therapies.

2020-07-15 | GSE146117 | GEO

A modular differentiation system maps multiple human kidney lineages from pluripotent stem cells [scRNA-Seq]

2020-07-15 | GSE146118 | GEO

Cadherin adhesion complexes direct cell aggregation in the epithelial transition of Wnt-induced nephron progenitor cells

Project description:The aggregation of nephron progenitor cells (NPC) is required to form the nephron precursor renal vesicle (RV) as they undergo the mesenchymal-to-epithelial transition (MET). Canonical Wnt signaling regulates the MET of NPCs via the effector molecule β-catenin. β-catenin acts as a transcriptional co-activator during the differentiation of NPCs, however, if it has any role as an adhesion regulating molecule via the cadherin-catenin complex is currently unknown. Using in vitro NPC culture system with gene editing and modulated Wnt signaling input, we investigated the morphological transition of NPCs and its underlying mechanism modeling the initial step of the MET in vivo. Increasing Wnt signaling input with the small molecule agonist CHIR resulted in the aggregation of NPCs similar to the generation of the nephron anlagen. By removing β- and α-catenin from the NPCs, NPCs are sorted out from these aggregates, demonstrating the key role of the cadherin-catenin complex in the aggregation. β-catenin was essential for the induction, however, the removal of α-catenin did not affect the transcriptional profile of NPCs. Removal of extracellular Ca2+ resulted in the transient loss of cell-cell contacts suggesting the role of cadherins in the aggregation process. The analysis of in vitro bulk RNA-seq cadherin expression profile matched the in vivo cadherin expression profile determined by single-cell RNA-seq. The combined removal of pre-existing and inducible cadherins phenocopied the results of β- and α-catenin KO experiments highlighting the crucial role of the cadherin-catenin complex by multiple lines of evidence. Notably, the induction of NPCs is independent of their aggregation. The in vitro modeling of nephron development provides a mechanistic understanding how cell adhesion is regulated via the cadherin-catenin complex during nephrogenesis.

2024-07-29 | GSE232606 | GEO

GLS2 links glutamine metabolism and atherosclerosis by remodelling artery walls (aorta).

Project description:Metabolic dysregulation, including perturbed glutamine-glutamate homeostasis, is common in atherosclerotic cardiovascular disease. Here, we reveal that modulation of glutaminolysis or glutamate availability in culture media is critical for smooth muscle cell line (MOVAS) phenotypic switching. Cells were treated for 24 hours with glutaminase inhibitors (50mM DON, Sigma-SML0601) in presence or absence of 2mM glutamate suplementation (Gibco-35050061). High-throughput transcriptional profiling revealed that modulation of glutamine and glutamate homeostasis impacted genes involved in protein and extracellular matrix organization, cell motility and microtubule. Thus, we uncovered a novel role for glutamine metabolism in the phenotypic switch in SMCs, a hallmark of vascular remodelling.

2024-10-17 | GSE270058 | GEO

GLS2 links glutamine metabolism and atherosclerosis by remodelling artery walls (MOVAS).

2024-10-17 | GSE270056 | GEO

Transcriptomics of mouse bone marrow erythropoiesis

Project description:Metabolic requirements vary during tissue development, but little is known whether and how metabolic rewiring orchestrates lineage differentiation and maturation. We discovered an essential metabolic switch from glutamine catabolism to glutamine synthesis during erythropoiesis. Glutamine synthetase (GS), one of the oldest functioning genes, is induced during terminal maturation to promote detoxification of ammonia generated during heme biosynthesis, which is massively upregulated to support hemoglobin production. Loss of GS in mouse erythroid precursors causes ammonia accumulation, oxidative stress, leading to maturation arrest and apoptosis. In β-thalassemia, GS activity is impaired by protein oxidation, causing glutamate and ammonia accumulation, whereas enforced GS expression alleviates the metabolic and pathologic defects. These results identify an evolutionarily conserved metabolic adaptation that may be leveraged to treat common red cell disorders.

2024-11-15 | GSE226078 | GEO

Multiomics analysis couples mRNA turnover and translational control of glutamine metabolism to the differentiation of the activated CD4+ T cell

Project description:The ZFP36 family of RNA-binding proteins acts post-transcriptionally to repress translation and promote RNA decay. Studies of genes and pathways regulated by the ZFP36 family in CD4+ T cells have focussed largely on cytokines, but their impact on metabolic reprogramming and differentiation is unclear. Using CD4+ T cells lacking Zfp36 and Zfp36l1, we combined the quantification of mRNA transcription, stability, abundance and translation with crosslinking immunoprecipitation and metabolic profiling to determine how they regulate T cell metabolism and differentiation. Our results suggest that ZFP36 and ZFP36L1 act directly to limit the expression of genes driving anabolic processes by two distinct routes: by targeting transcription factors and by targeting transcripts encoding rate-limiting enzymes. These enzymes span numerous metabolic pathways including glycolysis, one-carbon metabolism and glutaminolysis. Direct binding and repression of transcripts encoding glutamine transporter SLC38A2 correlated with increased cellular glutamine content in ZFP36/ZFP36L1-deficient T cells. Increased conversion of glutamine to α-ketoglutarate in these cells was consistent with direct binding of ZFP36/ZFP36L1 to Gls (encoding glutaminase) and Glud1 (encoding glutamate dehydrogenase). We propose that ZFP36 and ZFP36L1 as well as glutamine and α-ketoglutarate are limiting factors for the acquisition of the cytotoxic CD4+ T cell fate. Our data implicate ZFP36 and ZFP36L1 in limiting glutamine anaplerosis and differentiation of activated CD4+ T cells, likely mediated by direct binding to transcripts of critical genes that drive these processes.

2021-04-28 | GSE155087 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data