Expression data of Gata4 endothelial cell-subtype specific knockout whole liver lysates
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PROVIDER: PRJNA591646 | ENA |
REPOSITORIES: ENA
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Project description:Liver sinusoidal endothelial cells (LSEC) constitute discontinuous, permeable microvessels, with a characteristic program of gene expression that differs significantly from continuous microvascular endothelial cells e.g. in the lung. Gata4 is described as master regulator of LSEC specification during liver development. Here, we sought to analyze the role of endothelial Gata4 in the adult liver. We used microarrays to analyse the program of gene expression in murine whole liver lysates with LSEC-specifig Gata4 deficiency.
2020-09-15 | GSE141003 | GEO
Project description:Liver sinusoidal endothelial cells (LSEC) constitute discontinuous, permeable microvessels, with a characteristic program of gene expression that differs significantly from continuous microvascular endothelial cells e.g. in the lung. Gata4 is described as master regulator of LSEC specification during liver development. Here, we sought to analyze the role of endothelial Gata4 in the adult liver. We used microarrays to analyse the program of gene expression in murine liver endothelial cells with Gata4 deficiency.
2020-09-15 | GSE141001 | GEO
Project description:Expression data of Gata4 endothelial cell-subtype specific knockout primary murine liver sinusoidal endothelial cells
| PRJNA591647 | ENA
Project description:Cardiac malformations due to aberrant development of the atrioventricular (AV) valves are among the most common forms of congenital heart disease. At localized swellings of extracellular matrix known as the endocardial cushions, the endothelial lining of the heart undergoes an epithelial to mesenchymal transition (EMT) to form mesenchymal progenitors of the AV valves. Further growth and differentiation of these mesenchymal precursors results in formation of portions of the atrial and ventricular septae, and generation of thin, pliable valves. The transcription factor Gata4 is expressed in the endothelium and mesenchyme of the AV valves. Using a Tie2-Cre transgene, we selectively inactivated Gata4 within endothelial-derived cells. Mutant endothelium failed to undergo EMT, resulting in hypocellular cushions. Mutant cushions had decreased levels of Erbb3, an EGF-family receptor essential for EMT in the atrioventricular cushions. In Gata4 mutant embryos, Erbb3 downregulation was associated with impaired activation of Erk, which is also required for EMT. Expression of a Gata4 mutant protein defective in interaction with Friend of Gata (FOG) cofactors rescued the EMT defect, but resulted in decreased proliferation of mesenchyme and hypoplastic cushions that failed to septate the ventricular inlet. We demonstrate two novel functions of Gata4 in development of the AV valves. First, Gata4 functions as an upstream regulator of an Erbb3-Erk pathway necessary for EMT, and second, Gata4 acts to promote cushion mesenchyme growth and remodeling. Experiment Overall Design: To further investigate the role of Gata4 in EC development, we specifically inactivated Gata4 in endothelium and endothelium-derived cushion mesenchyme. All mice were maintained in a mixed C57BL6/129 genetic background. Gata4wt/flox; T2Cre+ mice were crossed with Gata4flox/flox mice to yield Gata4flox/flox (CONTROL); T2Cre+ (Gata4T2del) (MUTANT) mice.
2008-06-13 | E-GEOD-5298 | biostudies-arrayexpress
Project description:Overall goal: To elucidate the endothelial-specific role of Gata4 signaling in endothelial maturation and vascular maintenance. Purpose of analysis: To generate a transcriptional profile of Gata4-deficient endothelial cells in the adult myocardium under homeostatic conditions.
2018-12-25 | GSE109661 | GEO
Project description:Angiocrine signaling by liver sinusoidal endothelial cells (LSEC) regulates liver functions such as liver growth, metabolic maturation, and regeneration. Recently, we identified GATA4 as the master regulator of LSEC specification during development. Here, we studied endothelial GATA4 in the adult liver and in hepatic disease pathogenesis. We generated adult Clec4g-icretg/0xGata4fl/fl (Gata4LSEC KO) mice with deficiency of Gata4 in LSEC. Livers were analyzed by histology, electron microscopy, immunohistochemistry/immunofluorescence, in-situ hybridization, and by expression profiling and ATAC-sequencing of isolated LSEC. For liver regeneration, partial hepatectomy was performed. As models of liver fibrosis, CDAA diet and chronic CCl4 exposure were applied. Human single cell RNAseq data sets were analyzed for endothelial alterations in healthy and cirrhotic livers. Genetic Gata4 deficiency in LSEC in adult mice caused perisinusoidal liver fibrosis, hepatopathy and impaired liver regeneration. Sinusoidal capillarization and LSEC-to-continuous endothelial transdifferentiation were accompanied by a profibrotic angiocrine switch including de novo endothelial expression of hepatic stellate cell-activating cytokine PDGFB. Increased chromatin accessibility and amplification by activated Myc mediated angiocrine PDGFB expression. In CDAA diet-induced perisinusoidal liver fibrosis, LSEC showed repression of GATA4, activation of MYC and the profibrotic angiocrine switch already detected in Gata4LSEC KO mice. Comparison of CDAA-fed Gata4LSEC KO and control mice demonstrated that endothelial Gata4 indeed protects from dietary-induced perisinusoidal liver fibrosis. In human cirrhotic livers, Gata4-positive LSEC and endothelial Gata4 target genes were reduced, while non-LSEC endothelial cells and Myc target genes including PDGFB were enriched. Endothelial GATA4 protects from perisinusoidal liver fibrosis by repressing MYC activation and profibrotic angiocrine signaling on the chromatin level. Therapies targeting the GATA4/MYC/PDGFB/PDGFRβ axis offer a promising strategy for the prevention and treatment of liver fibrosis.
2020-10-21 | GSE154827 | GEO
Project description:Angiocrine signaling by liver sinusoidal endothelial cells (LSEC) regulates liver functions such as liver growth, metabolic maturation, and regeneration. Recently, we identified GATA4 as the master regulator of LSEC specification during development. Here, we studied endothelial GATA4 in the adult liver and in hepatic disease pathogenesis. We generated adult Clec4g-icretg/0xGata4fl/fl (Gata4LSEC KO) mice with deficiency of Gata4 in LSEC. Livers were analyzed by histology, electron microscopy, immunohistochemistry/immunofluorescence, in-situ hybridization, and by expression profiling and ATAC-sequencing of isolated LSEC. For liver regeneration, partial hepatectomy was performed. As models of liver fibrosis, CDAA diet and chronic CCl4 exposure were applied. Human single cell RNAseq data sets were analyzed for endothelial alterations in healthy and cirrhotic livers. Genetic Gata4 deficiency in LSEC in adult mice caused perisinusoidal liver fibrosis, hepatopathy and impaired liver regeneration. Sinusoidal capillarization and LSEC-to-continuous endothelial transdifferentiation were accompanied by a profibrotic angiocrine switch including de novo endothelial expression of hepatic stellate cell-activating cytokine PDGFB. Increased chromatin accessibility and amplification by activated Myc mediated angiocrine PDGFB expression. In CDAA diet-induced perisinusoidal liver fibrosis, LSEC showed repression of GATA4, activation of MYC and the profibrotic angiocrine switch already detected in Gata4LSEC KO mice. Comparison of CDAA-fed Gata4LSEC KO and control mice demonstrated that endothelial Gata4 indeed protects from dietary-induced perisinusoidal liver fibrosis. In human cirrhotic livers, Gata4-positive LSEC and endothelial Gata4 target genes were reduced, while non-LSEC endothelial cells and Myc target genes including PDGFB were enriched. Endothelial GATA4 protects from perisinusoidal liver fibrosis by repressing MYC activation and profibrotic angiocrine signaling on the chromatin level. Therapies targeting the GATA4/MYC/PDGFB/PDGFRβ axis offer a promising strategy for the prevention and treatment of liver fibrosis.
2020-10-21 | GSE154824 | GEO
Project description:Cardiac malformations due to aberrant development of the atrioventricular (AV) valves are among the most common forms of congenital heart disease. At localized swellings of extracellular matrix known as the endocardial cushions, the endothelial lining of the heart undergoes an epithelial to mesenchymal transition (EMT) to form mesenchymal progenitors of the AV valves. Further growth and differentiation of these mesenchymal precursors results in formation of portions of the atrial and ventricular septae, and generation of thin, pliable valves. The transcription factor Gata4 is expressed in the endothelium and mesenchyme of the AV valves. Using a Tie2-Cre transgene, we selectively inactivated Gata4 within endothelial-derived cells. Mutant endothelium failed to undergo EMT, resulting in hypocellular cushions. Mutant cushions had decreased levels of Erbb3, an EGF-family receptor essential for EMT in the atrioventricular cushions. In Gata4 mutant embryos, Erbb3 downregulation was associated with impaired activation of Erk, which is also required for EMT. Expression of a Gata4 mutant protein defective in interaction with Friend of Gata (FOG) cofactors rescued the EMT defect, but resulted in decreased proliferation of mesenchyme and hypoplastic cushions that failed to septate the ventricular inlet. We demonstrate two novel functions of Gata4 in development of the AV valves. First, Gata4 functions as an upstream regulator of an Erbb3-Erk pathway necessary for EMT, and second, Gata4 acts to promote cushion mesenchyme growth and remodeling. Keywords: genetic modification
2006-07-14 | GSE5298 | GEO
Project description:The aim of this study was to induce cardiomyogenic conversion of Human Umbilical Vein Endothelial Cells (HUVEC ) by triggering ectopic expression of the cardiac transcription factors Nkx2.5 and GATA4. Cells were cultured without cell myocardial co-culture system and transduced with lentivirus containing coding sequence of Nkx2.5, GATA4 or GFP as control. Cells were cultured in the EBM-2/ EGM-2 medium, 12 days before microarray analysis. We report in this study that over-expression of NKX2.5 and GATA4 in HUVECs stimulates the expression of some specific genes important in the cardiomyogenic differentiation process, leading to partial switch of these cells from the endothelial to the myocardial course. 12 arrays were analysed. Three competitive hybridizations to the arrays were performed in duplicate using each time, two dye-swap following this experimental design: AWA065 : CY5 (HUVEC+NKX2,5) / CY3 (HUVEC) AWA067 : CY5 (HUVEC) / CY3 (HUVEC+NKX2,5) AWA075 : CY5 (HUVEC+NKX2,5) / CY3 (HUVEC) AWA076 : CY5 (HUVEC) / CY3 (HUVEC+NKX2,5) AWA068 : CY5 ((HUVEC) / CY3 (HUVEC+GATA4) AWA070 : CY5 (HUVEC+GATA4) / CY3 ((HUVEC) AWA073 : CY5 (HUVEC+GATA4) / CY3 ((HUVEC) AWA002 : CY5 ((HUVEC) / CY3 (HUVEC+GATA4) AWA066 : CY5 (HUVEC) / CY3 (HUVEC+NKX2.5+GATA4) AWA069 : CY5 (HUVEC+NKX2.5+GATA4) / CY3 (HUVEC) AWA071 : CY5 (HUVEC+NKX2.5+GATA4) / CY3 (HUVEC) AWA074 ; CY5 (HUVEC) / CY3 (HUVEC+NKX2.5+GATA4)
2012-04-20 | E-GEOD-37459 | biostudies-arrayexpress
Project description:Liver sinusoidal endothelial cells (LSEC) represent a unique, organ-specific type of discontinuous endothelial cells. LSEC instruct the hepatic vascular niche by paracrine-acting angiocrine factors. Recently, we have shown that LSEC-specific transcriptional regulator GATA4 induces expression of BMP2 in cultured endothelial cells (EC) in vitro. Furthermore, angiocrine Bmp2 signaling in the liver in vivo was demonstrated to control iron homeostasis. Here, we investigated GATA4-dependent autocrine BMP2 signaling in endothelial cells by gene expression profiling. GATA4 induced a large cluster of inflammatory endothelial response genes in cultured EC, which is similar to previously identified virus-induced and interferon-associated responses. Treating the cells with the BMP2 inhibitor Noggin counter-regulated the GATA4-dependent inflammatory phenotype of EC, indicating that BMP2 is indeed the major driver. In contrast to continuous EC, LSEC were less prone to activation by BMP2. Notably, GATA4-dependent induction of the inflammatory EC response gene cluster was attenuated by over-expression of the LSEC-specific transcriptional modifier LMO3 while hepatocyte activation was fully preserved, indicating conserved BMP2 synthesis. In summary, our data suggest that transcriptional counter-regulation by GATA4 and LMO3 in LSEC prevents autocrine induction of an inflammatory phenotype, while maintaining angiocrine BMP2-mediated cell communication in the liver vascular niche.
2017-07-13 | GSE100711 | GEO