Transcriptome profiling of GATA4 depleted hepatocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE49130 | GEO | 2013/11/07
SECONDARY ACCESSION(S): PRJNA213127
REPOSITORIES: GEO
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Project description:Analysis of changes in gene expression following hepatocyte specific deletion of GATA4 in adult mice. Results showed that the subset of differentially expressed genes had liver specific ontologies. Total RNA isolated from hepatocytes of AAV8-Tbg-Cre injected GATA4 fl/fl mice was compared to total RNA isolated from AAV-Tbg-GFP injected GATA4 fl/fl mice.
2013-11-07 | E-GEOD-49130 | biostudies-arrayexpress
Project description:Analysis of changes in gene expression following hepatocyte specific deletion of GATA4 and GATA6 in adult mice. Results showed that the subset of differentially expressed genes had liver specific ontologies.
2013-11-07 | GSE51478 | GEO
Project description:Analysis of changes in gene expression following hepatocyte specific deletion of GATA4 and GATA6 in adult mice. Results showed that the subset of differentially expressed genes had liver specific ontologies. Total RNA isolated from hepatocytes of AAV8-Tbg-Cre injected GATA4,6 fl/fl mice was compared to total RNA isolated from AAV-Tbg-GFP injected GATA4,6 fl/fl mice.
2013-11-07 | E-GEOD-51478 | biostudies-arrayexpress
Project description:GATA4 regulates the liver development, but it's function and the gene transcriptional programs it regulates in the adult liver is unknown. In this study, we determined the genome-wide occupancy sites of GATA4 by performing ChIP-seq of whole livers. We have identified 4409 GATA4 enrichment peaks using two peak calling methods and irreproducible discovery rate (IDR) analysis. This corresponds to 3075 genes with GATA4 peaks within -5 kb of transcription start site (TSS) and +5 kb of transcription termination site (TTS). MEME analysis shows that approximately 90% of the peaks have the WGATAR motif, suggesting direct binding by GATA4. The peaks containing the WGATAR motif have a ChIP-seq higher tag enrichment score than peaks lacking the motif. Genome Regions Enrichment of Annotations Tool (GREAT) analysis of genes bound by GATA4 identified ontologies with liver specific functions. In summary, our study shows for the first time genome-wide occupancy profile of GATA4in the adult mouse liver. ChIP-sequencing of whole mouse livers from 2-3 month old mice
2013-11-07 | E-GEOD-49131 | biostudies-arrayexpress
Project description:GATA4 regulates the liver development, but it's function and the gene transcriptional programs it regulates in the adult liver is unknown. In this study, we determined the genome-wide occupancy sites of GATA4 by performing ChIP-seq of whole livers. We have identified 4409 GATA4 enrichment peaks using two peak calling methods and irreproducible discovery rate (IDR) analysis. This corresponds to 3075 genes with GATA4 peaks within -5 kb of transcription start site (TSS) and +5 kb of transcription termination site (TTS). MEME analysis shows that approximately 90% of the peaks have the WGATAR motif, suggesting direct binding by GATA4. The peaks containing the WGATAR motif have a ChIP-seq higher tag enrichment score than peaks lacking the motif. Genome Regions Enrichment of Annotations Tool (GREAT) analysis of genes bound by GATA4 identified ontologies with liver specific functions. In summary, our study shows for the first time genome-wide occupancy profile of GATA4in the adult mouse liver.
2013-11-07 | GSE49131 | GEO
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 | GSE100712 | GEO
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
Project description:Microvascular endothelial cells (EC) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular EC instruct neighboring cells in their organ-specific vascular niches by angiocrine factors that comprise secreted growth factors/angiokines, but also extracellular matrix molecules and transmembrane proteins. The molecular regulators, however, that drive organ-specific microvascular transcriptional programs and thereby regulate angiodiversity, are largely elusive. Opposite to continuous barrier-forming EC, liver sinusoids are a prime model of discontinuous, permeable micro-vessels. Here, we show that transcription factor GATA4 controls liver sinusoidal endothelial (LSEC) specification and function. LSEC-restricted deletion of GATA4 caused transformation of discontinuous liver sinusoids into continuous capillaries. Capillarization was characterized by ectopic basement membrane deposition and formation of an abundantly VE-Cadherin expressing continuous endothelium. Correspondingly, ectopic expression of GATA4 in cultured continuous EC mediated downregulation of continuous EC transcripts and upregulation of LSEC genes. Regarding angiocrine functions, the switch from discontinuous LSEC to continuous EC during embryogenesis caused liver hypoplasia, fibrosis, and impaired colonization by hematopoietic progenitor cells resulting in anemia and embryonic lethality. Thus, GATA4 acts as master regulator of hepatic microvascular specification and acquisition of organ-specific vascular competence indispensable for liver development. The data also establish an essential role of the hepatic microvasculature for embryonic hematopoiesis.
2017-03-09 | GSE92352 | GEO
Project description:Microvascular endothelial cells (EC) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular EC instruct neighboring cells in their organ-specific vascular niches by angiocrine factors that comprise secreted growth factors/angiokines, but also extracellular matrix molecules and transmembrane proteins. The molecular regulators, however, that drive organ-specific microvascular transcriptional programs and thereby regulate angiodiversity, are largely elusive. Opposite to continuous barrier-forming EC, liver sinusoids are a prime model of discontinuous, permeable micro-vessels. Here, we show that transcription factor GATA4 controls liver sinusoidal endothelial (LSEC) specification and function. LSEC-restricted deletion of GATA4 caused transformation of discontinuous liver sinusoids into continuous capillaries. Capillarization was characterized by ectopic basement membrane deposition and formation of an abundantly VE-Cadherin expressing continuous endothelium. Correspondingly, ectopic expression of GATA4 in cultured continuous EC mediated downregulation of continuous EC transcripts and upregulation of LSEC genes. Regarding angiocrine functions, the switch from discontinuous LSEC to continuous EC during embryogenesis caused liver hypoplasia, fibrosis, and impaired colonization by hematopoietic progenitor cells resulting in anemia and embryonic lethality. Thus, GATA4 acts as master regulator of hepatic microvascular specification and acquisition of organ-specific vascular competence indispensable for liver development. The data also establish an essential role of the hepatic microvasculature for embryonic hematopoiesis.
2017-03-09 | GSE92356 | GEO
Project description:Microvascular endothelial cells (EC) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular EC instruct neighboring cells in their organ-specific vascular niches by angiocrine factors that comprise secreted growth factors/angiokines, but also extracellular matrix molecules and transmembrane proteins. The molecular regulators, however, that drive organ-specific microvascular transcriptional programs and thereby regulate angiodiversity, are largely elusive. Opposite to continuous barrier-forming EC, liver sinusoids are a prime model of discontinuous, permeable micro-vessels. Here, we show that transcription factor GATA4 controls liver sinusoidal endothelial (LSEC) specification and function. LSEC-restricted deletion of GATA4 caused transformation of discontinuous liver sinusoids into continuous capillaries. Capillarization was characterized by ectopic basement membrane deposition and formation of an abundantly VE-Cadherin expressing continuous endothelium. Correspondingly, ectopic expression of GATA4 in cultured continuous EC mediated downregulation of continuous EC transcripts and upregulation of LSEC genes. Regarding angiocrine functions, the switch from discontinuous LSEC to continuous EC during embryogenesis caused liver hypoplasia, fibrosis, and impaired colonization by hematopoietic progenitor cells resulting in anemia and embryonic lethality. Thus, GATA4 acts as master regulator of hepatic microvascular specification and acquisition of organ-specific vascular competence indispensable for liver development. The data also establish an essential role of the hepatic microvasculature for embryonic hematopoiesis.
2017-03-09 | GSE92354 | GEO