Project description:Tau (MAPT) is a microtubule-associated protein causing frequent neurodegenerative diseases or inherited frontotemporal lobar degenerations. Emerging evidence for non-canonical functions of Tau in DNA protection and P53 regulation suggests its involvement in cancer. Indeed, Tau expression correlates with cancer-specific survival or response to microtubule therapeutics. These data may imply common molecular pathways involved in the pathogenesis of neurodegenerative disorders and cancer. To bring new evidence that Tau represents a key protein in cancer, we present an in silico pan-cancer analysis of MAPT transcriptomic profile in over 11000 clinical samples and over 1300 pre-clinical samples provided by the TCGA and the DEPMAP datasets respectively. We completed this analysis by exploring a possible interplay of MAPT with wild-type or mutated P53. Then, we calculated the impact of MAPT expression on clinical outcome and drug response. Overall, the results support a relevant role of the MAPT gene in several cancer types, although the contribution of Tau to cancer appears to very much depend on the cellular context.
Project description:CRISPR/Cas9 system was used to generate mediator complex subunit 1 (MED1) knockout human pre-B ALL cell line 697. RNA-seq was performed to observe the effects of MED1 deletion on gene expression in 697.
Project description:In this study, we used the murine (Mus musculus) medullary thymic epithelial cell line (mTEC 3.10 cell line) co-cultured with fresh thymocytes as a functional assay for mTEC-thymocyte adhesion. Then we analyzed the differential transcriptional profile of this cell line, by means of Agilent oligo microarray hybridization, comparing Autoimmune regulator (Aire) wild-type cells vs Crispr-Cas9-induced Aire KO cells. The comparative transcriptional expression signatures allowed us to find those differentially expressed mRNAs or lncRNAs between the samples tested.
Project description:Annexin A1 (ANXA1) is a Ca2+-binding protein involved in pancreatic cancer (PC) progression. It is able to mediate cytoskeletal organization maintaining a malignant phenotype. ANXA1 Knock-Out (KO) MIA PaCa-2 cells partially lost their migratory and invasive capabilities and also the metastatization process is affected in vivo. Here, we investigated the microRNA (miRNA) profile in ANXA1 KO cells. The analysis of the modification in miRNA expression remarked the significant involvement of ANXA1 in PC progression. In this study, we focused on miR-196a which is a well known oncogenic factor in several tumour models and it appeared down-modulated in absence of ANXA1. Furthermore, both ANXA1 and miR-196a are able to trigger the mechanisms of the epithelial to mesenchymal transition (EMT). Our results show that the reintroduction of miR-196a through the mimic sequence restored the early aggressive phenotype of MIA PaCa-2. Then, ANXA1 seems to support the expression of miR-196a and its role. On the other hand, this miRNA is able to mediate some of protein functions in PC progression. This work elucidates the correlation between ANXA1 and specific miRNA sequences, particularly miR-196a, and provides new knowledge about the protein intracellular role.
Project description:Plants as non-mobile organisms constantly integrate varying environmental signals to flexibly adapt their growth and development. Local fluctuations in water and nutrient availability, sudden changes in temperature or other abiotic and biotic stresses can trigger changes in the growth of plant organs. Multiple mutually interconnected hormonal signaling cascades act as essential endogenous translators of these exogenous signals in the adaptive responses of plants. Although the molecular backbones of hormone transduction pathways have been identified, the mechanisms underlying their interactions are largely unknown. Here, using genome wide transcriptome profiling we identify an unknown auxin and cytokinin cross-talk component; SYNERGISTIC ON AUXIN AND CYTOKININ1 (SYAC1), whose expression in roots is strictly dependent on both of these hormonal pathways. We show that SYAC1 is a component of secretory pathway, whose enhanced activity interferes with deposition of cell wall components and can fine-tune organ growth and sensitivity to soil pathogens
Project description:Lambda interferons IFNL1-3 mediate antiviral immunity by inducing interferon sensitive genes (ISGs) in epithelial tissues. Contrarily, a variant creating the functional gene IFNL4 is associated with impaired clearance of hepatitis C virus (HCV) despite of higher liver expression of ISGs in untreated HCV patients. We aimed to explore IFNL4 signaling mechanism by comparing expression profiles from human hepatic cell line clones with genetic modifications influencing the ISG signaling pathway (IFNLR1/IL10R2 knockouts, IFNL4/IFNL3 expression stimulation by transfection).
Project description:ATAC-seq was performed, mapped, and analyzed as previously described (PMID: 34446717: \\"ATAC-seq was performed on 50,000 cells per replicate as described in Buenrostro et al. (with modifications based on Corces et al.), on EpiSCs and PSM-differentiated cell populations at desired time-points. Libraries were generated using the Ad1_noMX and Ad2.1–2.16 barcoded primers64 and amplified for 10 total PCR cycles. Libraries were purified with AMPure XP beads to remove contaminating primer dimers and fragments >1,000 bp. Library quality was assessed using the Fragment analyzer and quantitated by Qubit assay. The libraries were sequenced with 50 bp paired-end reads on a Next-Seq 500 Sequencer (Illumina) at the DanStem Genomics Platform (University of Copenhagen, Copenhagen, Denmark).\\"). For all conditions, two biological replicate samples were collected from independent experiments. Library quality was assessed using the Fragment Analyzer and quantitated by Qubit assay. The libraries were sequenced with 50 bp paired-end reads on a NextSeq 500 Sequencer (Illumina) at the DanStem/reNEW Genomics Platform (University of Copenhagen, Copenhagen, Denmark). Prediction of cis-regulatory elements (CREs) and gene annotation was done using rGREAT (v4.0.4) [PMID: 20436461],[PMID: 36040971] or HOMER (v.4.7)[PMID: 20513432]