This SuperSeries is composed of the SubSeries listed below.
The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition.
Age, Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2.
Specimen part, Treatment
View SamplesEndothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under pro-inflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT promoting pro-inflammatory and hypoxic conditions. Silencing of JMJD2B reduced TGF-β2-induced expression of mesenchymal genes and prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting pro-inflammatory and hypoxic conditions and support the acquirement of a mesenchymal phenotype.
The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition.
Age, Cell line, Treatment
View SamplesImpaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulates endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is up-regulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function.
The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2.
No sample metadata fields
View SamplesImpaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulates endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is up-regulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function.
The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2.
No sample metadata fields
View SamplesCells were reprogrammed from cardiac fibroblasts to cardiomyocytes, in various conditions. These are the iCM cells (induced cardiomyocytes). There are both human and mouse arrays here, as seen below.
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program.
Specimen part, Treatment
View SamplesOBJECTIVE: To study the genetic regulatory mechanisms in the remote zone of left ventricular (LV) free wall in order to partly explain the more frequent progression to heart failure after acute myocardial infarction (AMI) in diabetic rats.
The accelerated post-infarction progression of cardiac remodelling is associated with genetic changes in an untreated streptozotocin-induced diabetic rat model.
Sex, Age, Specimen part
View SamplesCardiomyocyte-like cells can be reprogrammed from somatic fibroblasts by combinations of genes, providing a new avenue for cardiac regenerative therapy. Here we show that functional cardiomyocytes can be rapidly and efficiently generated from human fibroblasts by specific combination small molecules. Microarray analysis has been used to compare the expression profile of cardiomyocyte-like cells derived from human foreskin and lung fibroblasts, and human ES cell-derived cardiomyocytes.
Conversion of human fibroblasts into functional cardiomyocytes by small molecules.
Specimen part
View SamplesNeonatal hearts (P2) from wildtype, miR-1-1 null and miR-1-2 +/-: miR-1-1 +/- double heterozygote animals were isolated and total RNA was extracted with TRIzol (Invitrogen), following the manufacturers suggested protocol.
microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart.
Specimen part
View Samples