Filters
Technology
Platform
GSE30694
Bos taurus
33 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Interferon tau (IFNT), a Type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal, produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In study one, endometrial tissue samples were obtained on days (D) 12, 15, and 18 post-mating from nonpregnant or pregnant heifers. In study two, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or placebo lipid extrudates or PBS only as controls. Endometrial biopsies were collected after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Study one revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In study two, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the datasets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. Vice versa, genes were found as differentially expressed during pregnancy but not after IFNA2 treatment. In study three, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT.
Publication Title
Comparison of the effects of early pregnancy with human interferon, alpha 2 (IFNA2), on gene expression in bovine endometrium.
Sample Metadata Fields
Sex, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Gene 2.0 ST Array (hugene20st)
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.
Publication Title
GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
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.
Publication Title
GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Microvascular endothelial cells (EC) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific EC control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal EC (LSEC) are uniquely differentiated to fulfil important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSEC. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSEC using EC subtype-specific Stab2-Cre mice. Genetic inactivation of hepatic angiocrine Bmp2 signaling in Stab2-Cre;Bmp2fl/fl (Bmp2LSECKO) mice caused massive iron overload in the liver, and increased serum iron levels and iron deposition in several organs similar to classic hereditary hemochromatosis. Iron overload was mediated by decreased hepatic expression of hepcidin, a key regulator of iron homeostasis. Thus, angiocrine Bmp2 signaling within the hepatic vascular niche represents a constitutive pathway indispensable for iron homeostasis in vivo that is non-redundant with Bmp6. Notably, we demonstrate that organ-specific angiocrine signaling is essential not only for the homeostasis of the respective organ, but also for the homeostasis of the whole organism.
Publication Title
Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human testicular cells were isolated mechanically and enzymatically from testis of braindead donors and from urological samples. The expression of genes was studied at baseline and 1,25(OH)2D treated conditions.
Publication Title
Testicular synthesis and vitamin D action.
Sample Metadata Fields
Specimen part
View Samples