Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors [bulk RNA-Seq]

ABSTRACT: Cancers of the gastrointestinal tract including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia are common comorbidities of obesity. Excessive delivery of macronutrients to the cells lining the gut can increase one’s risk for these cancer by inducing imbalances in the rate of intestinal stem cell proliferation vs. differentiation, which can produce polyps and other aberrant growths. We demonstrate that serine palmitoyltransferase (SPT), which diverts dietary fatty and amino acids into the sphingolipid biosynthesis pathway, is a critical modulator of intestinal stem cell homeostasis. SPT and other enzymes in the biosynthetic pathway are upregulated in human colon tumors. These enzymes produce sphingolipids that serve as pro-stemness signals that stimulate peroxisome-proliferator activated receptor alpha (PPARa)-mediated induction of fatty acid binding protein-1. This increases fatty acid uptake and oxidation and enhances the stemness program. Serine palmitoyltransferase thus serves as a critical link between dietary macronutrients, epithelial regeneration, and cancer risk.

ORGANISM(S): Mus musculus

PROVIDER: GSE188674 | GEO | 2022/11/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors [single cell RNA-Seq]

Project description:Cancers of the gastrointestinal tract including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia are common comorbidities of obesity. Excessive delivery of macronutrients to the cells lining the gut can increase one’s risk for these cancer by inducing imbalances in the rate of intestinal stem cell proliferation vs. differentiation, which can produce polyps and other aberrant growths. We demonstrate that serine palmitoyltransferase (SPT), which diverts dietary fatty and amino acids into the sphingolipid biosynthesis pathway, is a critical modulator of intestinal stem cell homeostasis. SPT and other enzymes in the biosynthetic pathway are upregulated in human colon tumors. These enzymes produce sphingolipids that serve as pro-stemness signals that stimulate peroxisome-proliferator activated receptor alpha (PPARa)-mediated induction of fatty acid binding protein-1. This increases fatty acid uptake and oxidation and enhances the stemness program. Serine palmitoyltransferase thus serves as a critical link between dietary macronutrients, epithelial regeneration, and cancer risk.

2022-11-01 | GSE188675 | GEO

Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors.

Project description:Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors.

| PRJNA779920 | ENA

Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors [bulk RNA-Seq]

Project description:Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors [bulk RNA-Seq]

| PRJNA779929 | ENA

Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors [single cell RNA-Seq]

Project description:Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors [single cell RNA-Seq]

| PRJNA779928 | ENA

Carnitine Palmitoyltransferase 1 facilitates fatty acid oxidation in a noncell autonomous manner [CPT1a_RNAseq]

Project description:Mitochondrial fatty acid oxidation is facilitated by the combined activities of Carnitine Palmitoyltransferase 1 and Carnitine Palmitoyltransferase 2 which generate and utilize acylcarnitines respectively. We compared the response of mice with liver specific deficiencies in the liver enriched Cpt1a or the ubiquitous Cpt2 and discovered that they display unique metabolic, physiological and molecular phenotypes. The loss of Cpt1a or Cpt2 resulted in the induction of the muscle enriched isoenzyme, Cpt1b, in hepatocytes in a Ppara dependent manner. Primary component analysis also revealed overall differential grouping between mouse with deletions of either Cpt1a or Cpt2. Our results utilize stringent genetic mouse models to elucidate that the sequential steps to facilitate mitochondrial fatty acid oxidation may have other factors.

2024-05-31 | GSE267915 | GEO

Carnitine Palmitoyltransferase 1 facilitates fatty acid oxidation in a noncell autonomous manner [TKO_RNAseq]

Project description:Mitochondrial fatty acid oxidation is facilitated by the combined activities of Carnitine Palmitoyltransferase 1 and Carnitine Palmitoyltransferase 2 which generate and utilize acylcarnitines respectively. We compared the response of mice with liver specific deficiencies in Cpt1a and Cpt1b, Cpt2, or the triple deletion of all three acyltransferases. We discovered that they display unique metabolic, physiological and molecular phenotypes. The loss of Cpt1a and Cpt1b or Cpt2 resulted in particular transcriptional outputs in hepatocytes. We show that much of the transcriptional signature is suppressed when deleting both Cpt2 and Ppara, showing the contribution of Ppara. Our results utilize stringent genetic mouse models to characterize the differential phenotypes of mice lacking Cpt1a and Cpt1b or Cpt2 and also show the contribution of a major transcription factor, Ppara.

2024-05-31 | GSE267916 | GEO

Carnitine Palmitoyltransferase 1 facilitates fatty acid oxidation in a noncell autonomous manner [CPT1a_RNAseq]

Project description:Carnitine Palmitoyltransferase 1 facilitates fatty acid oxidation in a noncell autonomous manner [CPT1a_RNAseq]

| PRJNA1113636 | ENA

Carnitine Palmitoyltransferase 1 facilitates fatty acid oxidation in a noncell autonomous manner [TKO_RNAseq]

Project description:Carnitine Palmitoyltransferase 1 facilitates fatty acid oxidation in a noncell autonomous manner [TKO_RNAseq]

| PRJNA1113638 | ENA

Sphingolipid-dependent Dscam sorting regulates axon segregation

Project description:Neurons are highly polarized cells with distinct protein compositions in axonal and dendritic compartments. Cellular mechanisms controlling polarized protein sorting have been described for mature nervous system but little is known about the segregation in newly differentiated neurons. In a forward genetic screen for regulators of Drosophila brain circuit development, we identified mutations in <span style="color: rgb(54, 54, 54); font-style: normal; font-weight: 400; background-color: rgb(245, 245, 245);">Serine Palmitoyltransferase </span>(SPT), an evolutionary conserved enzyme in sphingolipid biosynthesis. Here we show that reduced levels of sphingolipids in SPT mutants cause axonal morphology defects similar to loss of cell recognition molecule Dscam. Loss- and gain-of-function studies show that neuronal sphingolipids are critical to prevent aggregation of axonal and dendritic Dscam isoforms, thereby ensuring precise Dscam localization to support axon branch segregation. Furthermore, SPT mutations causing neurodegenerative HSAN-I disorder in humans also result in formation of stable Dscam aggregates and axonal branch phenotypes in Drosophila neurons, indicating a causal link between developmental protein sorting defects and neuronal dysfunction.

2019-03-29 | MTBLS825 | MetaboLights

1-deoxysphingolipid synthesis compromises anchorage-independent growth and plasma membrane endocytosis in cancer cells

Project description:Serine palmitoyltransferase (SPT) predominantly incorporates serine and fatty acyl-CoAs into diverse sphingolipids that serve as structural components of membranes and signaling molecules within or amongst cells. However, SPT also uses alanine as a substrate in the contexts of low serine availability, alanine accumulation, or diseasecausing mutations in hereditary sensory neuropathy type I (HSAN1), resulting in the synthesis and accumulation of 1-deoxysphingolipids. These species promote cytotoxicity in neurons and impact diverse cellular phenotypes, including suppression of anchorage-independent cancer cell growth. While altered serine and alanine can promote 1-deoxysphingolipid synthesis, they impact numerous other metabolic pathways important for cancer cells. Here we combined isotope tracing, quantitative metabolomics, and functional studies to better understand the mechanistic drivers of 1- deoxysphingolipid toxicity in cancer cells. Both alanine treatment and SPTLC1 C133W expression induce 1-deoxy(dihydro)ceramide synthesis and accumulation but fail to broadly impact intermediary metabolism, abundances of other lipids, or growth of adherent cells. However, spheroid culture and soft agar colony formation were compromised when endogenous 1-deoxysphingolipid synthesis was induced via SPTLC1 C133W expression. Consistent with these impacts on anchorageindependent cell growth, we observed that 1-deoxysphingolipid synthesis reduced plasma membrane endocytosis. These results highlight a potential role for SPT promiscuity in linking altered amino acid metabolism to plasma membrane endocytosis.

2022-08-31 | ST002274 | MetabolomicsWorkbench

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