Tmem67 knock-out mouse model of Meckel-Gruber syndrome type 3 (MKS3, MIM #607361) and Joubert syndrome type (JBTS6, #610688): investigation into differential gene expression in the early post-natal (P0) cerebullum
Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects.
No sample metadata fields
View SamplesIL-2R signaling is essential for regulatory T cell (Treg) function. However, the precise contribution for IL-2 during Treg thymic development, peripheral homeostasis, and lineage stability remains unclear. Here we show that IL-2R signaling is essential for thymic Tregs at an early step for expansion/survival and a later step for functional maturation. Using selective deletion of CD25 in peripheral Tregs, we also find that IL-2R signaling was absolutely essential for their persistence whereas Treg lineage stability was IL-2-independent. CD25 knockout peripheral Tregs showed increased apoptosis, oxidative stress, signs of mitochondrial dysfunction, and reduced transcription of key enzymes of lipid and cholesterol biosynthetic pathways. A divergent IL-2 transcriptional signature was noted for thymic Tregs versus peripheral Tregs. These data indicate that IL-2R signaling in the thymus and the periphery leads to distinctive effects on Treg function, where peripheral Treg survival depends on a non-conventional mechanism of metabolic regulation. Overall design: To evaluate IL-2Ra-dependent transcriptional activity in thymic Tregs, CD25 KO Tregs were isolated from thymuses of Treg-targeted CD25 conditional KO animals, as well as CD25 WT controls. Groups of 5 biological replicates (mice) were compared. To evaluate IL-2Ra-dependent transcriptional activity in splenic Tregs, CD25 KO Tregs were isolated from tamoxifen-inducible, Treg-targeted CD25 conditional KO mice as well as CD25 WT reporter controls following tamoxifen induction. Groups of 4 biological replicates (mice) were compared. Libraries were prepared using KAPA's RNA Hyperprep protocol and sequenced on a 75 bp paired-end run using the Illumina NextSeq 500 High Output Kit (150-cycle; 400 M flow cell). Reads from RNA-seq were mapped to the Mus musculus genome GRCm38 using STAR (ver.2.5.0) aligner. Raw counts were generated based on Ensembl genes (GENCODE M13) with featureCounts (ver.1.5.0). Differentially expressed genes between CD25 KO and WT Tregs were identified using DESeq2, and determined by a threshold of false discovery rate (FDR) <0.01.
Essential and non-overlapping IL-2Rα-dependent processes for thymic development and peripheral homeostasis of regulatory T cells.
Specimen part, Cell line, Subject
View SamplesPrimary effusion lymphoma is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposis sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients yet efforts to develop superior therapeutic approaches have been impeded by lack of animal models that more accurately mimic human disease. To address this issue we developed a direct xenograft model, UM-PEL-1, by transferring freshly-isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth. We utilized this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. Transcriptome analysis by genomic arrays revealed that bortezomib downregulated cell cycle progression, DNA replication, and Myc-target genes.
Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma.
Cell line
View SamplesmRNA expression profiling of pancreatic cancer, comparing adjacent normal tissue, patient tumour and first generation patient derived xenograft tumours
Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.
Specimen part
View SamplesSchizophrenia-associated miRNA were bidirectionally modulated in HEK-293, HeLa, and SH-SY5Y cell models. Results provide important insights into the current understanding of miRNA function in various cellular environments.
Alternative mRNA fates identified in microRNA-associated transcriptome analysis.
Cell line, Treatment
View SamplesResistance of Calu3 NSCLC cells to the cytotoxic nucleoside analog gemcitabine (2',2'-difluorodeoxycytidine) can be prevented as well as reversed by the rexinoid X receptor selective agonist bexarotene. This study was designed to investigate the changes in gene expression associated with gemcitabine resistance and its reversal by bexarotene. In addition to the parental Calu3 cells and the 10 cycles of treatment of the gemcitabine resistant Calu3 cells with vehicle or bexarotene, analogous treatment paradigms with gemcitabine alone as well as the combination of both compounds have been included as controls. (However, it has to be noted that in the combination treatment, cells that were re-sensitized by bexarotene have largely been removed from the culture before harvest due to the cytotoxic activity of gemcitabine.)
Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification.
No sample metadata fields
View SamplesInhibition of the costimulatory CD40-CD40L receptor/ligand dyad drastically reduces atherosclerosis. However, its long-term blockage can result in immune suppression. We recently identified small molecule inhibitors that block the interaction between CD40 and TNF Receptor Associated Factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity. Here we further characterized the working mechanisms of TRAF-STOPs 6877002 and 6860766 in atherogenesis.
Targeting CD40-Induced TRAF6 Signaling in Macrophages Reduces Atherosclerosis.
Specimen part, Treatment
View SamplesGene expression analysis of yw follicles at S9/10a, S10B, S12, and S14; Gene expression analysis of pxt mutant follicles (f01000 and EY03052) at S10B, S12, S14
Drosophila eggshell production: identification of new genes and coordination by Pxt.
Sex, Specimen part
View SamplesYoung individuals possess distinct properties that adults do not. The juvenile animals show higher activities for growth, healing, learning and plasticity than adults. The machinery for establishing these juvenile properties is not fully understood. To better understand the molecular constituents for the above properties, we performed a comprehensive transcriptome analysis of differently aged cells of mice by high-throughput sequencing. The samples are isolated mouse hepatocytes and caridomyocytes in triplicate. As a result, we identified the genes selectively highly expressed in the young cells. These genes, collectively called as juvenility-associated genes (JAGs), show significant enrichments in the functions such as alternative splicing, phosphorylation and extracellular matrix (ECM). This implies the juvenescence might be achieved by these functions at the cell level. The JAG mutations are associated with progeria syndromes and growth disorders. Thus, the JAGs might organize the juvenile property of young animals and analysis of JAGs may provide scientific and therapeutic approaches toward treating the genetic diseases.
Identification of juvenility-associated genes in the mouse hepatocytes and cardiomyocytes.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition.
Specimen part, Cell line, Treatment
View Samples