Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A niche-dependent redox rheostat regulates epithelial stem cell fate

ABSTRACT: Intestinal stem cells (ISCs) reside in regionally variable niches that provide diverse microenvironmental cues such as tissue oxygen status, and morphogen signaling. Integration of these cues with ISC metabolism and fate remains poorly understood. Here, we show that cellular redox balance orchestrates niche factors with metabolic state to govern cell fate decisions. We demonstrate that hypoxia and Wnt signaling synergistically restrict the reactive oxygen species generating enzyme NADPH oxidase 1 (NOX1) regionally to the crypt base in the distal colon. NOX1 enables maintenance of an oxidative cell state that licenses cell cycle entry, altering the balance of asymmetric ISC self-renewal and lineage commitment. Mechanistically, cell redox state directs a self-reinforcing circuit that connects hypoxia inducible factor 1-dependent signaling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1. Our studies show redox balance acts as a cellular rheostat that is central and causative for metabolic control of the ISC cell-cycle.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Primary Cell, Colon

SUBMITTER: Qianni Peng

LAB HEAD: Eranthie Weerapana

PROVIDER: PXD065916 | Pride | 2025-12-03

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	NOX1_NS_oxICAT_.msf	Msf
	NOX1_NS_oxICAT_1_01.raw	Raw
	NOX1_NS_oxICAT_1_02.raw	Raw
	NOX1_NS_oxICAT_2_01.raw	Raw
	NOX1_NS_oxICAT_2_02.raw	Raw

Items per page:

1 - 5 of 27

Similar Datasets

Combining redox proteomics with proximity labeling to monitor localized cysteine oxidation

Project description:Reactive oxygen species (ROS) can modulate protein function through cysteine oxidation. Identifying targets of ROS can provide insight into uncharacterized ROS-regulated pathways. Several redox-proteomic workflows, such as OxICAT, exist to identify sites of cysteine oxidation. However, determining ROS targets localized within subcellular compartments and ROS hotspots remains challenging with existing workflows. Here, we present a chemoproteomic platform, PL-OxICAT, which combines proximity labeling (PL) with OxICAT to monitor localized cysteine oxidation events. We show that TurboID-based PL-OxICAT can monitor cysteine oxidation events within subcellular compartments such as the mitochondrial matrix and intermembrane space. Furthermore, we use APEX-based PL-OxICAT to monitor oxidation events within ROS hotspots by using endogenous ROS as the source of peroxide for APEX activation. Together, these platforms further hone our ability to monitor cysteine oxidation events within specific subcellular locations and ROS hotspots and provide a deeper understanding of the protein targets of endogenous and exogenous ROS.

2024-05-21 | PXD034118 | Pride

Protein expression and oxidation in the hippocampus of neuronal nucleoredoxin knockout (Nestin-NXN-/-) versus floxed control mice (NXN-flfl)

Project description:Nucleoredoxin (NXN) is a thioredoxin-like member of the large group of redoxins which maintain redox balances in the cell. Its primary localization is the cytoplasm, and it is highly expressed in neurons. It has been described as a redox regulator of WNT signaling via maintenance of the redox balance of Disheveled (Dvl). Previous proteomic analyses in NXN-knockdown SH-SY5Y cells found a high fraction of reduced proteins involved in development and cell differentiation. The results suggested NXN mainly acted as oxidase under the culture conditions. The functions in vivo are not known, but full deletion of NXN is embryonically lethal owing to cranial deformities. We have generated mice with a pan-neuronal Nestin-Cre driven deletion of NXN (Nestin-NXN-/-) to study its functions in neurons. Nestin-NXN-/- develop normally and are healthy up to old age. They show a loss of exploratory and playful behavior but have no deficits of cognitive functions, social behavior or readouts of anxiety. Using a Yeast-2-Hybrid screen, calcium calmodulin kinase 2a was identified as interaction partner. Camk2a is crucial for long-term potentiation and thereby learning and memory but is also associated with psychiatric diseases, and it is regulated via redox modification of cysteines that impact on the autophosphorylation status of a critical threonine. Camk2a colocalized and co-precipitated with NXN and its activity depended on the presence of NXN. To further study the functions of NXN in neurons we performed a proteomic screen of the hippocampal proteome and the redox proteome using the BIAM switch method.

2021-09-10 | PXD024624 | Pride

A niche-dependent redox rheostat regulates epithelial stem cell fate in the distal colon II

Project description:The niche environment surrounding intestinal stem cells (ISCs) varies along the length of intestine and provides key cues that regulate stem cell fate. Here, we investigated the role of cellular redox balance in colonic ISC function. We show that hypoxia and Wnt signaling synergize to restrict the reactive oxygen species (ROS) generating enzyme NADPH oxidase 1 (NOX1) to the crypt base in the distal colon. NOX1 function maintains a more oxidative cell state that licenses cell cycle entry, altering the balance of asymmetric stem cell self-renewal and directing lineage commitment. Mechanistically, cell redox state directs a self-reinforcing circuit that connects hypoxia inducible factor 1 (HIF1a)-dependent signaling with regulation of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1). Our studies show that cellular redox balance is a central and niche-dependent regulator of epithelial homeostasis and regeneration and provide a basis for understanding disease propensity in the distal large intestine.

2025-02-17 | GSE289397 | GEO

A niche-dependent redox rheostat regulates epithelial stem cell fate in the distal colon

2025-02-17 | GSE289209 | GEO

Quantification of oxidized proteins in wild type and Nox2 deficient mouse dorsal root ganglia

Project description:Here we studied the NOX2 dependent redox-proteome in dorsal root ganglia in mice. The overall goal was to assess the degree of NOX2-dependent changes in oxidised proteins following exposure to enriched enviroment and sciatic nerve axotomy in dorsal root ganglia.

2020-10-13 | PXD018085 | Pride

Analysis of ageing-dependent thiol oxidation reveals early oxidation of proteins involved in core proteostasis functions

Project description:Oxidants have a profound impact on biological systems in physiology and under pathological conditions. Oxidative post-translational modifications of protein thiols are well-recognized as a readily occurring alteration of proteins. Changes in protein thiol redox state can modify the function of proteins and thus can control cellular processes. However, chronic oxidative stress causes oxidative damage to proteins with detrimental consequences for cellular function and organismal health. The development of techniques enabling the site-specific and quantitative assessment of protein thiol oxidation on a proteome-wide scale significantly expanded the number of known oxidation-sensitive protein thiols. However, lacking behind are large-scale data on the redox state of proteins during ageing, a physiological process accompanied by increased levels of endogenous oxidants. Here, we present the landscape of protein thiol oxidation in chronologically aged wild-type Saccharomyces cerevisiae in a time-dependent manner. Our data determine early oxidation targets in key biological processes governing the de novo production of proteins, folding, and protein degradation. Comparison to existing datasets reveals evolutionary conservation of early oxidation targets. To facilitate accessibility and cross-species comparison of the experimental data obtained, we created the OxiAge Database, a free online tool for the research community that integrates current datasets on thiol redoxomes in aged yeast, nematode Caenorhabditis elegans, fruit fly Drosophila melanogaster, and mouse Mus musculus.

2024-02-07 | PXD042047 | Pride

Effects of the antibacterial compund Allicin from garlic on Escherichia coli

Project description:Allicin (diallyl thiosulfinate) from garlic is a highly potent natural antimicrobial substance. It inhibits growth of a variety of microorganisms, among them antibiotic resistant strains. Here, we show that upon exposure to allicin, growth of Escherichia coli is strongly inhibited. Growth inhibition coincides with a significant drop of total sulfhydryl concentrations and induction of the heat shock and oxidative stress response. In contrast to diamide, a potent inducer of disulfide stress, allicin does not induce cystine bond formation in proteins such as cytoplasmically expressed alkaline phosphatase PhoA. We identified and quantified the allicin-induced modification S-allylmercapto-cysteine for a set of cytoplasmic proteins by using a combination of label-free mass spectrometry and differential OxICAT labeling. Activity of isocitrate lyase AceA, an S-allylmercapto-modified candidate protein, is largely inhibited by allicin treatment in vivo. Our results indicate that the mode of action of allicin is a combination of disturbance of the redox balance and inactivation of crucial metabolic enzymes.

2016-05-02 | PXD003063 | Pride

Monitoring of protein thiol-oxidation in S.aureus USA300 under hypochlorite stress using OxICAT approach.

Project description:During infections, S. aureus has to cope with the oxidative burst of activated macrophages and neutrophils, including reactive oxygen and nitrogen species (RNS, ROS) and the strong oxidant hypochloric acid. We aimed to understand the global thiol-redox state in the major pathogen S. aureus and discover new NaOCl-sensitive proteins driven by thiol-switches. Thus, we performed a quantitative redox proteomics approach based on OxICAT and analyzed the percentages of thiol-oxidation levels in S.aureus before and after sub-lethal doses of 150 µM NaOCl stress. In parallel, we searched for protein S-bacillithiolation.

2016-12-22 | PXD004918 | Pride

Vav proteins orchestrate a keratinocyte auto/paracrine program critical for skin tumorigenesis.

Project description:Cutaneous squamous tumors rely on autocrine/paracrine loops for proper fitness. Targeting this Achilles’ heel is therefore considered a potential avenue for patient treatment. However, the mechanisms that engage and sustain such programs during tumor ontogeny are poorly understood. Here, we show that two Rho/Rac activators, the exchange factors Vav2 and Vav3, control the expression of an epithelial autocrine/paracrine program that regulates keratinocyte survival and proliferation as well as the creation of an inflammatory microenvironment. Vav proteins are also critically involved in some of the subsequent autocrine signaling loops activated in keratinocytes. The genetic inactivation of both Vav proteins reduces tumor multiplicity without hampering skin homeostasis, thus suggesting that pan-specific Vav therapies may be useful in skin tumor prevention and treatment. The dorsal skin of WT and DKO mice (Vav2-/-;Vav3-/-) were treated with either one or four applications of phorbol ester 12-O-tetradecanoylphorbol-13 acetate (TPA) (6.8 nmol in 200 μl acetone) two days after shaving. As control, we applied 200 μl of acetone. Animals were euthanized 24 hours after treatment.

2013-07-30 | E-GEOD-40849 | biostudies-arrayexpress

Quantifying changes in the bacterial thiol redox proteome during host-pathogen interaction

Project description:In this study, we used a quantitative redox proteomic method (OxICAT) to assess the in vivo thiol oxidation status of phagocytized E. coli. The majority (65.5%) of identified proteins harbored thiols that were significantly oxidized (>30%) upon phagocytosis. A substantial number of these proteins are from major metabolic pathways or are involved in cell detoxification and stress response, suggesting a systemic breakdown of the bacterial cysteine proteome in phagocytized bacteria.

2019-01-07 | PXD011386 | Pride

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