White adipose tissue is primary involved in the response to insulin after feeding, while brain is not directly sensitive to insulin levels.
eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription.
Specimen part
View SamplesLiver is primary involved in the response to insulin after feeding. Hepatocytes activates a tightly controlled genetic programme where specific sets of genes are modulates in response to insulin, for activation of the anabolic pathways.
eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription.
Specimen part
View SamplesNeural stem/progenitor cells were isolated from the lateral ventricle wall of 4-6 week-old CD1 mice and grown as neurospheres under low density culture conditions. Test cells were transduced with bicistronic retroviral constructs for the over-expression of Bmi1 together with eGFP, and control cells were transduced with an empty vector construct expressing eGFP only. To identify genes, which are regulated by BMI1 in neural stem/progenitor cells, the gene expression profiles of neurosphere cells over-expressing Bmi1 were compared empty vector control cells using Affymetrix Gene mouse ST1.0 arrays
The putative tumor suppressor gene EphA7 is a novel BMI-1 target.
Specimen part
View SamplesWe used microarrays to characterize the global changes in gene expression within the ascending aorta of mice due to conditional disruption of TGF- signaling in smooth muscle and/or due to heterozygous fibrillin-1 mutation.
Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis.
Age, Specimen part
View SamplesWe have used microarrays to identify individual genes and pathways regulated by Gq/11 or G12/13 signalling in type II alveolar epithelial cells isolated from the lungs of knockout mice.
Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33-mediated macrophage polarization and emphysema.
Specimen part
View SamplesRecurrent chromosomal translocations involving the mixed lineage leukemia gene (MLL) give rise to highly aggressive acute leukemia associated with poor clinical outcomes. The preferential involvement of chromatin-associated factors in MLL rearrangements belies a dependency on transcriptional control. To identify new targets for therapeutic development in MLL, we performed a genome-scale CRISPR-Cas9 knockout screen in MLL-AF4 leukemia. Among validated targets, we identified the transcriptional regulator, ENL, as an unrecognized dependency particularly indispensable for proliferation. To explain the mechanistic role for ENL in leukemia pathogenesis and the dynamic role in transcription control, we pursued a chemical genetic strategy utilizing targeted protein degradation. ENL loss suppresses transcription initiation and elongation genome-wide, with pronounced effects at genes featuring disproportionate ENL load. Importantly, ENL-dependent leukemic growth was contingent upon an intact YEATS epigenomic reader domain. These findings reveal a novel dependency in acute leukemia and a first mechanistic rationale for disrupting YEATS domains in disease. Overall design: RNA-seq in MV4;11 (Cas9; ENL-FKBP(F36V); ENL -/-) cells with dTAG-13 and EPZ-5676 treatment
Transcription control by the ENL YEATS domain in acute leukaemia.
Cell line, Subject
View SamplesThe aim of the RNA-seq was to identify the KMT9 transcriptome in PC-3M cells. The MCF10A breast epithelial cells that do not express KMT9a were used to show that the siRNA against KMT9 show no off-target effects. Overall design: 12 samples correponding to 4 times 3 replicates were used for the study
KMT9 monomethylates histone H4 lysine 12 and controls proliferation of prostate cancer cells.
Specimen part, Cell line, Treatment, Subject
View SamplesWe used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of cancer stem cell properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing Overall design: Single cells from three different populations: 30 cells from G1 cell cycle phase cultured in adherent conditions, 46 cells with low proliferation cultured in non-adherent conditions (mammosphere assasy), 45 cells with high proliferation cultured in non-adherent conditions (mammosphere assay)
Erratum: Identification of Breast Cancer Stem Cell Related Genes Using Functional Cellular Assays Combined With Single-Cell RNA Sequencing in MDA-MB-231 Cells.
Cell line, Subject
View SamplesThe vascular endothelium forms a physical barrier between blood and the surrounding tissue. Its constant exposure to haemodynamic shear stress controls endothelial barrier function which is of major importance for vascular homeostasis. The role of long non-coding RNAs (lncRNAs) in this process remains elusive. Here we identify the shear stress-induced lncRNA LASSIE (linc00520) as a stabilizer of adherens junctions (AJs) in endothelial cells (ECs), that is indispensable for normal endothelial barrier function and shear stress sensing. Silencing of LASSIE in ECs resulted in impaired cell survival, loss of cell-cell contacts and failure to align in the direction of flow. RNA affinity purification followed by mass spectrometry identified several junction proteins associated with LASSIE, including the endothelial adhesion protein PECAM-1 and intermediate filament (IF) protein nestin. Proteomic analysis of VE-cadherin-associated proteins showed that LASSIE silencing reduces VE-cadherin interaction with nestin and microtubule (MT)-associated cytoskeletal proteins. We confirmed that LASSIE silencing results in a decreased connection between VE-Cadherin and the cytoskeleton, resulting in loss of barrier function and shear stress sensing. Together, this study identifies the shear stress-induced lncRNA LASSIE as a critical link between AJs and the IF cytoskeleton, which is indispensable for normal EC junction stabilization and shear stress sensing.
Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function.
Specimen part
View SamplesThe nipple is an example of specialized epidermis. The unique epidermal stratification and gene expression is induced and maintained by developmental distinct fibroblast populations.
Estrogen modulates mesenchyme-epidermis interactions in the adult nipple.
Sex, Specimen part
View Samples