Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA sequencing of WT and Uhrf1 KO iNKT cells

ABSTRACT: Deletion of Uhrf1 resulted in stage 1-specific defects during iNKT cell development. To investigate the molecular mechanism, we sorted WT and Uhrf1-KO stage 1 iNKT cells and performed RNA-seq. By comparing gene expression profile, we found metabolic defects in Uhrf1-KO stage 1 iNKT cells. The expression of CD71 (Tfrc), two subunits of CD98 (Slc3a2 and Slc7a5) and Glut3 (Slc2a3) was reduced in stage 1 iNKT cells. Besides, the downstream pathways of AKT-mTOR axis were significantly reduced. Collectively, our results suggest that Uhrf1 is required for iNKT cell development by regulating the Akt-mTOR signaling pathway. We first sorted WT and Uhrf1-KO stage 1 iNKT cells, extracted the mRNA and performed RNA-seq. We then analyzed the differentially expressed genes and performed KEGG pathway analysis. We used RT-PCR to verify the expression of the key nutrient related genes (Tfrc, Slc3a2, Slc7a5 and Slc2a3) and used flow cytometry to test the protein level of metabolic related molecules. Besides, we also analyzed the expression of genes of mTOR downstream pathways to demonstrate that Uhrf1 mediated AKt-mTOR axis regulates iNKT cell development.

ORGANISM(S): Mus musculus

SUBMITTER: Yu Cui

PROVIDER: E-GEOD-77941 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

RNA sequencing of WT and Uhrf1 KO iNKT cells

Project description:Deletion of Uhrf1 resulted in stage 1-specific defects during iNKT cell development. To investigate the molecular mechanism, we sorted WT and Uhrf1-KO stage 1 iNKT cells and performed RNA-seq. By comparing gene expression profile, we found metabolic defects in Uhrf1-KO stage 1 iNKT cells. The expression of CD71 (Tfrc), two subunits of CD98 (Slc3a2 and Slc7a5) and Glut3 (Slc2a3) was reduced in stage 1 iNKT cells. Besides, the downstream pathways of AKT-mTOR axis were significantly reduced. Collectively, our results suggest that Uhrf1 is required for iNKT cell development by regulating the Akt-mTOR signaling pathway.

2016-03-10 | GSE77941 | GEO

Kidins220 and Aiolos promote thymic iNKT cell development by reducing TCR signals

Project description:Development of T cells is controlled by the signal strength of the TCR. The scaffold protein Kinase D-interacting substrate of 220 kDa (Kidins220) binds to the TCR; however, its role in T cell development was unknown. Here, we show that T cell-specific Kidins220 knock-out (T-KO) mice have strongly reduced invariant natural killer T (iNKT) cell numbers and modest decreases in conventional T cells. Enhanced apoptosis due to increased TCR signaling in T-KO iNKT thymocytes of developmental stage 2 and 3 shows that Kidins220 downregulates TCR signaling at these stages. scRNAseq indicated that the transcription factor Aiolos is downregulated in Kidins220-deficient iNKT cells. Analysis of an Aiolos KO demonstrated that Aiolos is a downstream effector of Kidins220 during iNKT cell development. In the periphery, T-KO iNKT cells show reduced TCR signaling upon stimulation with α-galactosylceramide, suggesting that Kidins220 promotes TCR signaling in peripheral iNKT cells. Thus, Kidins220 reduces or promotes signaling dependent on the iNKT cell developmental stage.

2024-03-11 | GSE253196 | GEO

Mus musculus

Project description:RNA sequencing of WT and Uhrf1 KO iNKT cells

| PRJNA312175 | ENA

Integrated molecular characterization of patient-derived models reveals therapeutic strategies for treating CIC-DUX4 sarcoma.

Project description:Capicua–double homeobox 4 (CIC-DUX4) rearranged sarcomas (CDSs) are extremely rare, highly aggressive primary sarcomas that represent a major therapeutic challenge. To identify selective therapeutic targets of CDS, we performed RNA sequencing of primary tumor samples from patients, patient-derived xenografts (PDXs) and PDX-derived cell lines and we highlighted an HMGA2/IGF2BPs/IGF2/IGF1R/AKT-mTOR axis that characterizes CDS. This highly active axis confers to CDSs sensitivity to both trabectedin, which prevents HMGA proteins from binding to IGF2BP2/3 promoters, and PI3K/mTOR inhibitor NVP-BEZ235 (dactolisib). Combined treatments with trabectedin and NVP-BEZ235 completely abolish the activation of the IGF2/IGF1R/AKT/mTOR axis and the in vivo growth of CDS tumors. The development of representative PDXs and PDX-derived cell lines models has helped to identify the unique sensitivities of CDS towards AKT/mTOR inhibitors and trabectedin, revealing a mechanism-based therapeutic strategy to fight this lethal cancer.

2022-01-12 | GSE165032 | GEO

Expression data from thymic lymphomas of Lck-MyrAkt positive mice with WT or KD mTOR expression

Project description:Lck-MyrAkt2 mice develop spontaneous thymic lymphomas at approximately 100-200 days of age, driven in part by a consitutatively-active AKT (due to myristoylation). mTOR Knock Down mice were crossed with Lck-MyrAkt postive mice to model the affects of decreasing mTOR activity on tumors with an activated PI3K/AKT/MTOR pathway. Lck-Akt/mTOR KD mice had prolonged survival compared to the Lck-Akt/mTOR WT mice. We used microarrays to compare the transcriptome in thymic lymphomas between Lck-Akt positive, mTOR WT and Lck-Akt positive, mTOR KD mice. Four thymic lymphomas from Lck-Akt/mTOR WT mice were compared to three thymic lymphomas from Lck-Akt/mTOR KD mice.

2015-09-15 | E-MTAB-3242 | biostudies-arrayexpress

mTOR promotes zebrafish larvae fin regeneration through regulating macrophages activation and CaM-mTOR-dnm1l axis

Project description:To investigate the functional and mechanistic roles of mTOR in zebrafish larvae fin regeneration, we firstly examined the spatiotemporal expression of mTOR in larvae fin and established a mTOR knockout (mTOR-KO) transgenic fish line using CRISPER / Cas9 gene editing technology. Moreover, mTOR was essential for the activation of macrophages, which is a key factor in maintaining the regenerative repair process. We also demonstrated that mTOR knockdown attenuated the proliferative capacity of bud embryo cell during the regenerative phase, while cell apoptosis was not affected. RNA-sequence analysis showed changes in mitochondrial function and dnm1l was identified as the main regulatory factor during the fin regeneration stage. We further suggested that mTOR may promote mitochondrial fission to support bud embryo cell regeneration via CaM-mTOR-dnm1l axis.

2023-10-13 | GSE242949 | GEO

The protumor function of UHRF1 is linked to both the Akt signaling cascade and the epithelial-mesenchymal transition in esophageal cancer

Project description:The epigenetic factor UHRF1 is highly expressed in many types of cancers, however, the underlying mechanism remains elusive. Here we report an oncogenic function of UHRF1 in esophageal cancer(EC). UHRF1 was observed to be robustly expressed in EC cells. Knockdown of UHRF1 was achieved in two EC cell lines TE-10 and Kyse410 using a shRNA-mediated lentivirus system. Silencing of UHRF1 led to the inhibition of the proliferation and the mesenchymal phenotype as determined by the wound-healing and the invasion-in-matrigel assays. Transcriptome profile analysis revealed that two groups of the genes are significantly suppressed upon the UHRF1-shRNA expression. One group is linked to Akt signal pathway and the other is linked to the epithelial-mesenchymal transition. MK2206, an Akt inhibitor, could also inhibit the growth and the mesenchymal phenotype of EC cells. But interestingly, while UHRF1 deficiency resulted in the downregulation of EMT-associated genes such as ZEB2, vimentin and twist1, MK2206 inhibition of Akt activity only suppressed the expression of snail, suggesting that the control of the mesenchymal phenotype by UHRF1 does not rely on the AKT cascade. We conclude that the oncogenic function of UHRF1 is linked to the synergistic effect on the Akt signal cascade and the EMT-specific genes in EC cells.

2022-12-10 | GSE141781 | GEO

Gene expression profiling of WT or Dicer KO iNKT cells and T cells

Project description:iNKT cells are a T lymphocyte subset displaying an innate effector phenotype that is acquired through a thymic developmental program controlled by microRNAs (miRNAs). iNKT cells lacking all miRNAs by the deletion of Dicer (Dicer KO) are markedly reduced and display a complete maturation block. In this study, we sought to gain insight into the miRNA-regulated genetic program required for iNKT cell development. By systemic analysis, we identified transcripts differentially expressed between thymic WT or Dicer KO iNKT cells and targeted by the iNKT cell-specific miRNAs. TGF-βRII, a molecule critically implicated in iNKT cell maturation, was found upregulated in Dicer KO iNKT cells together with increased TGF-β-dependent signaling. miRNAs belonging to the paralog miR-106a~363, miR-106b~25 and miR-17~92 clusters were predicted to target TGF-βRII mRNA during iNKT cell development. Thymic iNKT cells lacking all three miRNA clusters displayed both increased TGF-βRII expression and signaling and a maturation block, recapitulating those found in Dicer KO iNKT cells. Consistently, inhibition of TGF-β-dependent signaling in the absence of miRNAs, by crossing TGF-βRII KO and Dicer KO mice, rescued iNKT cell maturation. Collectively, our results highlight a fundamental requirement of the modulation of TGF-β-dependent signaling by miRNAs for iNKT cell development

2016-11-17 | GSE79901 | GEO

Gene expression profiles of uhrf1 mutant zebrafish

Project description:UHRF1 (Ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 to hemimethylated DNA during replication, is essential for maintaining DNA methylation patterns during cell division and is suggested to direct additional repressive epigenetic marks. Uhrf1 mutation in zebrafish results in multiple embryonic defects including failed hepatic outgrowth, but the epigenetic basis of these phenotypes is not known. We find that DNA methylation is the only epigenetic mark that is depleted in uhrf1 mutants and make the surprising finding that despite the reduced organ size in uhrf1 mutants, genes regulating DNA replication and S-phase progression were highly upregulated. Further, there is a striking increase in BrdU incorporation in uhrf1 mutant cells, and they retained BrdU labeling over several days, indicating they are arrested in S-phase. Moreover, some of the label retaining nuclei co-localized with TUNEL positive nuclei, suggesting that arrested cells are responsible for apoptosis. Importantly, dnmt1 mutation phenocopies the S-phase arrest and hepatic outgrowth defects in uhrf1 mutants and Dnmt1 knock-down enhances the uhrf1 hepatic phenotype. Together, these data indicate that DNA hypomethylation is sufficient to generate the uhrf1 mutant phenotype by promoting an S-phase arrest. We thus propose that cell cycle arrest is a mechanism to restrict propagation of epigenetically deranged cells during embryogenesis. Genome-wide expression profiling was performed on 2 uhrf1 mutant and 2 wildtype zebrafish larvae (120 hours post fertilization) by using Zebrafish Genome Array (Affymetrix) according to manufacturer's instruction.

2015-02-09 | E-GEOD-55339 | biostudies-arrayexpress

Effect of SWELL1 (LRRC8a) gene deletion on gene expression in differentiated myotubes

Project description:Maintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism, however the molecular mechanosensor remains unknown. Here, we show that SWELL1 (LRRC8a) functionally encodes a swell-activated anion channel that regulates PI3K-AKT, ERK1/2, mTOR signaling, muscle differentiation, myoblast fusion, cellular oxygen consumption, and glycolysis in skeletal muscle cells. SWELL1 over-expression in SWELL1 KO myotubes boosts PI3K-AKT-mTOR signaling to supra-normal levels and fully rescues myotube formation. Skeletal muscle targeted SWELL1 KO mice have smaller myofibers, generate less force ex vivo, and exhibit reduced exercise endurance, associated with increased adiposity under basal conditions, and glucose intolerance and insulin resistance when raised on a high-fat diet, compared to WT mice. These results reveal that the SWELL1-LRRC8 complex regulates insulin-PI3K-AKT-mTOR signaling in skeletal muscle to influence skeletal muscle differentiation in vitro and skeletal myofiber size, muscle function, adiposity and systemic metabolism in vivo.

2020-08-22 | GSE156667 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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