Project description:This study investigates the function of FAS-AS1 in the regulation of nasopharyngeal carcinoma. GSEA analysis of RNA-seq data suggested FAS-AS1 participate in mitochondria regulation and mRNA alternative splicing
Project description:<div>Olive (Olea europaea) has a long history of medicinal and nutritional values own to it rich in polyphenol and fatty acids (FAs) in fruits. In order to better understand the biosynthesis important of these metabolites, we generated comprehensive Iso-Seq full-length and illumina RNA-seq transcriptome, and targeted metabolomics dataset of different olive fruits maturity. The targeted metabolomics by using both GC/MS and LC/MS were totally quantified 35 FAs and 13 polyphenols. Iso-Seq library was constructed and sequenced by PacBio Sequel System, and a total of 5,891,652 (10.55 G) with an average length of 1,791 subreads were obtained. 492,350 circular consensus sequences (CCSs) were formed after merging and error correction through subread comparison. Of the 492,350 CCSs, 399,263 were found to be full-length non chimera (FLNC) reads, and 187,517 consensus reads were finally obtained by using clustering algorithm of Iterative clustering for error (IEC). These multiomics data provide a foundation to elucidate the mechanisms regulating biosynthesis of polyphenol and FAs during the maturation of olive fruits.</div><div><br></div><div><div><b>GC-MS</b> protocols and data are reported in the current study <b>MTBLS855</b>.</div><div><br></div><div><span _ngcontent-jcp-c3="""" class=""ng-star-inserted""><b>Polyphenols UPLC-MS</b></span> protocols and data associated to this study are reported in <b><a href=""http://www.ebi.ac.uk/metabolights/editor/study/MTBLS814"">MTBLS814</a></b>.</div><div><br></div><div><b>Tyrosol only UPLC-MS</b> <span _ngcontent-iov-c3="""" class=""ng-star-inserted"">protocols and data associated to this study are reported in <b><a href=""http://www.ebi.ac.uk/metabolights/editor/study/MTBLS814""><a href=""https://www.ebi.ac.uk/metabolights/MTBLS1127"">MTBLS1127</a>.</a></b></span></div></div>
Project description:<div>Olive (<i>Olea europaea</i>) has a long history of medicinal and nutritional values own to it rich in polyphenol and fatty acids (FAs) in fruits. In order to better understand the biosynthesis important of these metabolites, we generated comprehensive Iso-Seq full-length and illumina RNA-seq transcriptome, and targeted metabolomics dataset of different olive fruits maturity. The targeted metabolomics by using both GC/MS and LC/MS were totally quantified 35 FAs and 13 polyphenols. Iso-Seq library was constructed and sequenced by PacBio Sequel System, and a total of 5,891,652 (10.55 G) with an average length of 1,791 subreads were obtained. 492,350 circular consensus sequences (CCSs) were formed after merging and error correction through subread comparison. Of the 492,350 CCSs, 399,263 were found to be full-length non chimera (FLNC) reads, and 187,517 consensus reads were finally obtained by using clustering algorithm of Iterative clustering for error (IEC). These multiomics data provide a foundation to elucidate the mechanisms regulating biosynthesis of polyphenol and FAs during the maturation of olive fruits.</div><div><b><br></b></div><div><b>Polyphenols UPLC-MS</b> protocols and data are reported in the current study <b>MTBLS814</b>.</div><div><br></div><div><b>GC-MS</b> protocols and data associated to this study are reported in <b><a href=""https://www.ebi.ac.uk/metabolights/MTBLS855"">MTBLS855</a></b>.</div><div><br></div><div><span _ngcontent-iov-c3="""" class=""ng-star-inserted""><b>Tyrosol only UPLC-MS</b> <span _ngcontent-iov-c3="""" class=""ng-star-inserted"">protocols and data associated to this study are reported in <b><a href=""https://www.ebi.ac.uk/metabolights/MTBLS1127"">MTBLS1127</a>.</b></span></span></div><div><br></div><div><br></div>
Project description:The first GSSM of V. vinifera was reconstructed (MODEL2408120001). Tissue-specific models for stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases.
Project description:<div>Olive (Olea europaea) has a long history of medicinal and nutritional values own to it rich in polyphenol and fatty acids (FAs) in fruits. In order to better understand the biosynthesis important of these metabolites, we generated comprehensive Iso-Seq full-length and illumina RNA-seq transcriptome, and targeted metabolomics dataset of different olive fruits maturity. The targeted metabolomics by using both GC/MS and LC/MS were totally quantified 35 FAs and 13 polyphenols. Iso-Seq library was constructed and sequenced by PacBio Sequel System, and a total of 5,891,652 (10.55 G) with an average length of 1,791 subreads were obtained. 492,350 circular consensus sequences (CCSs) were formed after merging and error correction through subread comparison. Of the 492,350 CCSs, 399,263 were found to be full-length non chimera (FLNC) reads, and 187,517 consensus reads were finally obtained by using clustering algorithm of Iterative clustering for error (IEC). These multiomics data provide a foundation to elucidate the mechanisms regulating biosynthesis of polyphenol and FAs during the maturation of olive fruits.</div><div><br><span _ngcontent-ook-c3= class=ng-star-inserted><span _ngcontent-jcp-c3= class=ng-star-inserted><span _ngcontent-iov-c3= class=ng-star-inserted><b>Tyrosol only UPLC-MS</b> <span _ngcontent-iov-c3= class=ng-star-inserted>protocols and data associated to this study are reported in the current study</span></span></span></span><b><span _ngcontent-ook-c3= class=ng-star-inserted><span _ngcontent-jcp-c3= class=ng-star-inserted><span _ngcontent-iov-c3= class=ng-star-inserted><span _ngcontent-iov-c3= class=ng-star-inserted> MTBLS1127.<br></span></span></span></span></b></div><div><span _ngcontent-jcp-c3= class=ng-star-inserted><div><b><br></b></div><div><b>Polyphenols UPLC-MS</b> protocols and <span _ngcontent-ook-c3= class=ng-star-inserted><span _ngcontent-jcp-c3= class=ng-star-inserted>data associated to this study are reported in</span></span> <a href=https://www.ebi.ac.uk/metabolights/MTBLS814><b>MTBLS814</b></a>.</div><div><br></div><div><b>GC-MS</b> protocols and data associated to this study are reported in <b><a href=https://www.ebi.ac.uk/metabolights/MTBLS855>MTBLS855</a></b>.</div><div><br></div></span></div>
Project description:The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration1-6. For instance, β-actin mRNA and its associated RNA binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs), to support localized β-actin synthesis, crucial for cell migration7-9. However, whether other mRNAs and RBPs also localize at FAs remains unclear. Here, we identify hundreds of mRNAs that are enriched at FAs (FA-mRNAs). FA-mRNAs share characteristics with stress granule (SG) mRNAs and are found in ribonucleoprotein (RNP) complexes with the SG RBP. Mechanistically, G3BP1 binds to FA proteins in an RNA-dependent manner, and its RNA-binding and dimerization domains, essential for G3BP1 to form RNPs in SG10, are required for FA localization and cell migration. We find that G3BP1 RNPs promote cell speed by enhancing FA protein mobility and FA size. These findings suggest a previously unappreciated role for G3BP1 RNPs in regulating FA function under non-stress conditions.
Project description:Functional CD8+ T cell immune response is critical for immune surveillance and host defense against infection and tumor. Epigenetic mechanisms associated with RNA modification in controlling CD8+ T cell response remain poorly understood. Here, by T cell-specific deletion of fat mass and obesity-associated protein (FTO), a critical N6-methyladenosine (m6A) demethylase, we revealed that FTO was indispensable for sufficient CD8+ T cell immune response and protective function. FTO ablation led to considerable cell death in activated CD8+ T cells, which was attributed to apoptosis. MeRIP-seq analysis identified the upregulated m6A modification on Fas mRNA in FTO deficient CD8+ T cells. Loss of FTO promoted Fas expression via enhancing the Fas mRNA stability dependent on m6A reader IGF2BP3. Mutation of the Fas m6A sites or knockdown IGF2BP3 could rescue the upregulated Fas expression and cell apoptosis caused by FTO ablation in CD8+ T cells. Our findings defined a novel epigenetic regulatory mechanism of FTO-mediated m6A modification in supporting CD8+ T cell immune responses, providing new insights into understanding the post-transcriptional regulation in CD8+ T cell immunological functions.
Project description:The EwingM-bM-^@M-^Ys sarcoma protein EWS belongs to the TET family (FUS/TLS, EWS, TAF15) of RNA and DNA binding proteins, implicated in DNA transcription, pre-mRNA splicing and maintenance of genomic integrity. Translocations of these genes are characteristic of particular neoplasias, including EwingM-bM-^@M-^Ys sarcoma. To identify physiological RNA targets of EWS, we performed in vivo cross-linking and immunoprecipitation followed by high-throughput RNA sequencing (HITS-CLIP/CLIP-Seq) in HeLa cells. Sequencing identified EWS binding sites characterized by guanosine-rich motifs in nearly 9000 genes, with particular enrichment in exonic regions near 5M-bM-^@M-^Y splice sites. Exon 6 of the Fas/CD95 receptor, which is alternatively spliced to generate isoforms with opposing activities in programmed cell death, was found as a prominent EWS CLIP target, as well as by chromatin-immunoprecipitation (ChIP) and functional analysis. Manipulation of EWS levels and mutation of EWS binding sites led to changes in alternative splicing consistent with EWS promoting exon 6 inclusion and leading to the synthesis of the pro-apoptotic Fas/CD95 isoform. Biochemical characterization of factors associated with FAS exon 6 are consistent with the notion that EWS binds to exonic sequences near the 5M-bM-^@M-^Y splice site and promotes the recruitment of U1snRNP, favoring also recognition of the upstream 3' splice site by U2AF and thus exon definition. Consistent with a role for EWS in the regulation of programmed cell death, cells depleted of EWS show decreased sensitivity to Fas-induced apoptosis. We discuss the potential implications of this novel function of EWS in EwingM-bM-^@M-^Ys sarcoma. CLIP-Seq analysis of EWS, with 2 biological replicates of EWS and one non-specific control
Project description:Analysis on gene expression between RA-induced WT, Fas^lpr/lpr, and Fas^gld/gld mice. Data shows different expression pattern between Fas^gld/gld joint and Fas^lpr/lpr(or WT) mice. The reseults indicate sFasL-dependent, but Fas-independent gene expression during AIA
Project description:Kilian2024 - Immune cell dynamics in Cue-Induced Extended Human Colitis Model
Single-cell technologies such as scRNA-seq and flow cytometry provide critical insights into immune cell behavior in inflammatory bowel disease (IBD). However, integrating these datasets into computational models for dynamic analysis remains challenging. Here, Kilian et al., (2024) developed a deterministic ODE-based model that incorporates these technologies to study immune cell population changes in murine colitis. The model parameters were optimized to fit experimental data, ensuring an accurate representation of immune cell behavior over time. It was then validated by comparing simulations with experimental data using Pearson’s correlation and further tested on independent datasets to confirm its robustness. Additionally, the model was applied to clinical bulk RNA-seq data from human IBD patients, providing valuable insights into immune system dynamics and potential therapeutic strategies.
Figure 4c, obtained from the simulation of human colitis model is highlighted here.
This model is described in the article:
Kilian, C., Ulrich, H., Zouboulis, V.A. et al. Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease. npj Syst Biol Appl 10, 69 (2024). https://doi.org/10.1038/s41540-024-00395-9
Abstract:
Single-cell-based methods such as flow cytometry or single-cell mRNA sequencing (scRNA-seq) allow deep molecular and cellular profiling of immunological processes. Despite their high throughput, however, these measurements represent only a snapshot in time. Here, we explore how longitudinal single-cell-based datasets can be used for deterministic ordinary differential equation (ODE)-based modelling to mechanistically describe immune dynamics. We derived longitudinal changes in cell numbers of colonic cell types during inflammatory bowel disease (IBD) from flow cytometry and scRNA-seq data of murine colitis using ODE-based models. Our mathematical model generalised well across different protocols and experimental techniques, and we hypothesised that the estimated model parameters reflect biological processes. We validated this prediction of cellular turnover rates with KI-67 staining and with gene expression information from the scRNA-seq data not used for model fitting. Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease.
This model was curated during the Hackathon hosted by BioMed X GmbH in 2024.