MicroRNA-520f regulates EMT, as it activates CDH1 (mRNA) and E-cadherin (protein) expression, and it suppresses tumor cell invasion. We have characterized miR-520f target genes through whole genome transcriptional profiling of miRNA transfected pancreas cancer cells (PANC-1).
miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting <i>ADAM9</i> and <i>TGFBR2</i>.
Cell line, Treatment
View SamplesSkeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training
Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes.
Age
View SamplesAlmost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomewide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (stable group), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (skewed group), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication.
Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype.
Sex, Specimen part, Disease
View SamplesMicroarrays were used to analyze the gene expression in endoscopic-derived intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) and controls
Strong Upregulation of AIM2 and IFI16 Inflammasomes in the Mucosa of Patients with Active Inflammatory Bowel Disease.
Specimen part, Disease
View SamplesExpression analysis of migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow
Nuclear receptors Nur77 and Nurr1 modulate mesenchymal stromal cell migration.
Specimen part
View SamplesThe goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint.
Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake.
Sex, Specimen part
View SamplesThe intercalated disc of cardiac myocytes is emerging as a crucial structure in the heart. Loss of intercalated disc proteins like N-cadherin causes lethal cardiac abnormalities, mutations in intercalated disc proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein-2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium. Complete loss of LIMP-2 in genetically engineered mice did not affect cardiac development; however these LIMP-2 null mice failed to mount a hypertrophic response to increased blood pressure but developed cardiomyopathy. Disturbed cadherin localization in these hearts suggested that LIMP-2 has important functions outside lysosomes. Indeed, we also find LIMP-2 in the intercalated disc, where it associates with cadherin. RNAi-mediated knockdown of LIMP-2 decreases the binding of phosphorylated b-catenin to cadherin, while overexpression of LIMP-2 has the opposite effect. Taken together, our data show that lysosomal integrated membrane protein-2 is crucial to mount the adaptive hypertrophic response to cardiac loading. We demonstrate a novel role for LIMP-2 as an important mediator of the intercalated disc.
Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy.
No sample metadata fields
View SamplesEarly during culture of primary mouse HSCs gene expression changes.
Gene expression profiling of early hepatic stellate cell activation reveals a role for Igfbp3 in cell migration.
Specimen part
View SamplesmRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting “mRNP code” determines the fate of any given mRNA and thus determines the gene regulation at the post-transcriptional level. The La-related protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA binding factors characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3´UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently to their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability. Overall design: RNAseq experiments of HEK293 cells which were transfected with siRNAs targeting LARP4B and firefly luciferase as controls. The experiment was performed in triplicates.
LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation.
No sample metadata fields
View SamplesWhile the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less understood. By dissecting border regions and combining single-cell RNA sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny and subsets displayed distinct self-renewal capacities upon depletion and repopulation. Single-cell and fate-mapping analysis both suggested there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in the healthy and diseased brain. Overall design: sample of WT choroid plexus, sample of WT dura mater, sample of WT enriched SDM, sample of WT whole brain, sample of 9 months old APP/PS1 mice, sample of 16 months old APP/PS1 mice, sample of 16 months old WT mice, sample of Irf8 KO whole brain, sample of Irf8 KO choroid plexus, sample of Irf8 WT whole brain, sample of Irf8 WT choroid plexus, sample of dura mater with standard protocol and with ActD protocol, sample of choroid plexus with standard protocol and ActD protocol.
A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment.
Specimen part, Cell line, Subject
View Samples