Ontology highlight
ABSTRACT:
PROVIDER: PRJEB16833 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1711810.fastq.gz | Fastqsanger.gz | |||
| ERR1711811.fastq.gz | Fastqsanger.gz | |||
| ERR1711812.fastq.gz | Fastqsanger.gz | |||
| ERR1711813.fastq.gz | Fastqsanger.gz | |||
| ERR1711804.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Combining deep-sequencing, proteomics, phosphoproteomics and functional screens to discover novel regulators of sphingolipid homeostasis
| PRJEB16740 | ENA
Project description:Sphingolipids are essential components of eukaryotic cells with important functions in membrane biology and cellular signaling. Their levels are tightly controlled and coordinated with the abundance of other membrane lipids. How sphingolipid homeostasis is achieved is not yet well understood. Studies performed primarily in yeast showed that the phosphorylation states of several enzymes and regulators of sphingolipid synthesis are important, although a global understanding for such regulation is lacking. Here, we used high-resolution mass-spectrometry-based proteomics and phosphoproteomics, in combination with data from a chemical genetic screen, to analyze the cellular response to sphingolipid synthesis inhibition. Our dataset reveals that changes in protein phosphorylation, rather than protein abundance, dominate the response to blocking sphingolipid synthesis. We identified Ypk1 signaling as a major pathway that is activated under these conditions, and we confirmed and identified Ypk1 targets. We also revealed key aspects of the cellular response to sphingolipid deprivation, including nodes that intersect with sterol metabolism and modification of lipid transport. Our data provide a rich resource for on-going mechanistic studies of key elements of the cellular response to the depletion of sphingolipid levels and the maintenance of sphingolipid homeostasis.
2016-12-23 | PXD003854 | Pride
Project description:Virus proliferation inside host cells relies on a diverse range of host machineries and is also restricted by the host through antiviral factors. The configuration of virus-dependency and antiviral factors determine the permissiveness of host cells to virus infection, however, overall differences between highly permissive and restrictive cellular states remain largely unexplored. Here we employed integrated omics analysis combining RNA-seq, proteomics, and phosphoproteomics to study determinants of virus permissiveness on a model system comprising multiple cellular states: highly permissive cells (HEK293T), steady-state cells (HEK293), and restrictive cells (interferon alpha (IFN-a) stimulated HEK293) due to their similar genetic background and distinct permissiveness. Our in-depth proteomics map across cellular states revealed pathway-level depletion of innate immune response and enrichment of anabolic processes in HEK293T cell. RNA-seq and proteomics results depicted dynamic regulations of IFN-α response across early/late timepoints, highlighting a group of robustly upregulated antiviral factors. In addition, phosphoproteomics uncovered extensive alterations of phosphorylation in IFN-a response. Integrated analysis of multi-level omics results identified putative regulators of infection, and we experimentally validated their roles in virus infection.
2024-05-20 | GSE267610 | GEO
Project description:Background: The family with sequence similarity 20-member C (FAM20C) kinase, a Golgi casein kinase, which is responsible for phosphorylating the majority of the extracellular phosphoproteins within S-x-E/pS motifs, and is fundamentally associated with multiple biological processes to maintain cell proliferation, biomineralization, migration, adhesion, and phosphate homeostasis. In dissecting how FAM20C regulates downstream molecules and potential mechanisms, however, there are multiple target molecules of FAM20C, particularly many phenomena remain elusive, such as changes in cell-autonomous behaviors, incompatibility in genotypes and phenotypes, and others. Methods: Here, assay for transposase-accessible chromatin using sequencing (ATAC-seq), RNA sequencing (RNA-seq), proteomics, and phosphoproteomics were performed in Fam20c-dificient osteoblasts and to facilitate an integrated analysis and determine the impact of chromatin accessibility, genomic expression, protein alterations, signaling pathway, and post translational modifcations. Results: By combining ATAC-seq and RNA-seq, we identified TCF4 and Wnt signaling pathway as the key regulators in Fam20c-dificient cells. Further, we showed Calpastatin/Calpain proteolysis system as a novel target axis for FAM20C to regulate cell migration and F-actin cytoskeleton by integrated analysis of proteomics and phosphoproteomics. Furthermore, Calpastatin/Calpain proteolysis system could negatively regulate the Wnt signaling pathway. Conclusion: These observations implied that Fam20c knockout osteoblasts would cause cell homeostatic imbalance, involving changes in multiple signaling pathways in the conduction system.
2023-09-11 | GSE233445 | GEO
Project description:Perturbation of tissue homeostasis accompanies a diversity of inflammatory pathologies and imposes metabolic constraints at the cellular level that elicit ER stress, protein misfolding, and cell death. In response to ER stress, cells initiate the unfolded protein response (UPR), which determines divergent cell fate decisions, either promoting recovery of ER proteostasis and cell survival or triggering programmed cell death. However, the mechanisms by which the UPR transitions from the adaptive to terminal state are not fully understood. To discover novel UPR pathway regulators that influence the outcome of cellular ER stress responses, we performed genome-scale genetic perturbations. Our genome-wide screens revealed that distinct sets of genes regulate UPR activity and maintenance of ER homeostasis. This expansive dataset provides a rich resource that can be leveraged to elucidate signaling crosstalk during ER stress and discover novel UPR regulators.
2021-02-17 | GSE146841 | GEO
Project description:The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. We have studied mice with an inactive S1P lyase gene and have found that, in addition to the expected increase of sphingoid base phosphates, other sphingolipids (including sphingosine, ceramide, and sphingomyelin) were substantially elevated in the serum and /or liver of these mice. This latter increase is consistent with a reutilization of the sphingosine backbone for sphingolipid synthesis due to its inability to exit the sphingolipid metabolic pathway. Furthermore, the S1P lyase deficiency resulted in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol. Even though lipids in serum and lipid storage were elevated in liver, adiposity was reduced in the S1P lyase-deficient mice. Microarray analysis of lipid metabolism genes in liver showed that the S1P lyase deficiency caused widespread changes in their expression pattern. These results demonstrate that S1P lyase is a key regulator of the levels of multiple sphingolipid substrates and reveal functional links between the sphingolipid metabolic pathway and other lipid metabolic pathways that may be mediated by shared lipid substrates and changes in gene expression programs. The disturbance of lipid homeostasis by altered sphingolipid levels may be relevant to metabolic diseases. Experiment Overall Design: RNA samples from liver for three sphingosine-1-phosphate lyase knock-out and three WT mice.
2010-02-05 | E-GEOD-18745 | biostudies-arrayexpress
Project description:FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Tregs). While mice exclusively express FOXP3 in Tregs, humans also transiently express FOXP3 in stimulated conventional CD4+ T cells (Tconvs). Mechanisms governing these distinct expression patterns remain unknown. Here, we performed CRISPR screens tiling the FOXP3 locus and targeting TFs in human Tregs and Tconvs to discover cis-regulatory elements (CREs) and trans-regulators of FOXP3. Tconv FOXP3 expression depended on a subset of Treg CREs and Tconv-selective positive (TcNS+) and negative (TcNS-) CREs. Combinatorial silencing of Tconv CREs revealed their epistatic logic. The CREs are occupied and regulated by TFs we identified as critical regulators of FOXP3. Finally, mutagenesis of murine TcNS- revealed that it is critical for restriction of FOXP3 expression to Tregs. We discover CRE and TF circuitry controlling FOXP3 expression and reveal evolution of mechanisms regulating a gene indispensable to immune homeostasis.
2025-11-13 | GSE286470 | GEO
Project description:FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Tregs). While mice exclusively express FOXP3 in Tregs, humans also transiently express FOXP3 in stimulated conventional CD4+ T cells (Tconvs). Mechanisms governing these distinct expression patterns remain unknown. Here, we performed CRISPR screens tiling the FOXP3 locus and targeting TFs in human Tregs and Tconvs to discover cis-regulatory elements (CREs) and trans-regulators of FOXP3. Tconv FOXP3 expression depended on a subset of Treg CREs and Tconv-selective positive (TcNS+) and negative (TcNS-) CREs. Combinatorial silencing of Tconv CREs revealed their epistatic logic. The CREs are occupied and regulated by TFs we identified as critical regulators of FOXP3. Finally, mutagenesis of murine TcNS- revealed that it is critical for restriction of FOXP3 expression to Tregs. We discover CRE and TF circuitry controlling FOXP3 expression and reveal evolution of mechanisms regulating a gene indispensable to immune homeostasis.
2025-11-13 | GSE286471 | GEO
Project description:An integrated approach combining genomics, proteomics and DNA methylation with functional profiling to define molecular features associated with epithelial to mesenchymal transition (EMT) states. Genomic DNA from 36 lung adenocarcinoma cell lines was bisulfite treated and analyzed on the Illumina Infinium HumanMethylation27K BeadChip
2014-12-08 | E-GEOD-63940 | biostudies-arrayexpress
Project description:FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Tregs). While mice exclusively express FOXP3 in Tregs, humans also transiently express FOXP3 in stimulated conventional CD4+ T cells (Tconvs). Mechanisms governing these distinct expression patterns remain unknown. Here, we performed CRISPR screens tiling the FOXP3 locus and targeting TFs in human Tregs and Tconvs to discover cis-regulatory elements (CREs) and trans-regulators of FOXP3. Tconv FOXP3 expression depended on a subset of Treg CREs and Tconv-selective positive (NS+) and negative (NS-) CREs. Combinatorial silencing of Tconv CREs revealed their epistatic logic. The CREs are occupied and regulated by TFs we identified as critical regulators of FOXP3. Finally, mutagenesis of murine NS- revealed that it is critical for restriction of FOXP3 expression to Tregs. We discover CRE and TF circuitry controlling FOXP3 expression and reveal cell and species-specific regulation of a gene indispensable to immune homeostasis.
2025-11-13 | GSE305063 | GEO