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GSE92357
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- Rattus norvegicus
- 56 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Not all patients with nerve injury develop neuropathic pain. The extent of nerve damage and age at the time of injury are two of the few risk factors identified to date. In addition, preclinical studies show that neuropathic pain variance is heritable. To define such factors further, we performed a large-scale gene profiling experiment which plotted global expression changes in the rat dorsal root ganglion in three peripheral neuropathic pain models. This resulted in the discovery that the potassium channel alpha subunit KCNS1, involved in neuronal excitability, is constitutively expressed in sensory neurons and markedly downregulated following nerve injury. KCNS1 was then characterized by an unbiased network analysis as a putative pain gene, a result confirmed by single nucleotide polymorphism association studies in humans. A common amino acid changing allele, the 'valine risk allele', was significantly associated with higher pain scores in five of six independent patient cohorts assayed (total of 1359 subjects). Risk allele prevalence is high, with 18-22% of the population homozygous, and an additional 50% heterozygous. At lower levels of nerve damage (lumbar back pain with disc herniation) association with greater pain outcome in homozygote patients is P = 0.003, increasing to P = 0.0001 for higher levels of nerve injury (limb amputation). The combined P-value for pain association in all six cohorts tested is 1.14 E-08. The risk profile of this marker is additive: two copies confer the most, one intermediate and none the least risk. Relative degrees of enhanced risk vary between cohorts, but for patients with lumbar back pain, they range between 2- and 3-fold. Although work still remains to define the potential role of this protein in the pathogenic process, here we present the KCNS1 allele rs734784 as one of the first prognostic indicators of chronic pain risk. Screening for this allele could help define those individuals prone to a transition to persistent pain, and thus requiring therapeutic strategies or lifestyle changes that minimize nerve injury.
Publication Title
Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Parathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Publication Title
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome-wide expression studies were performed on dermal fibroblasts from Sotos syndrome patients with a confirmed NSD1 abnormality and compared with age-sex matched controls.
Publication Title
Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sexually dimorphic genome-wide binding of retinoid X receptor alpha (RXRα) determines male-female differences in the expression of hepatic lipid processing genes in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of gender differential gene expression levels in mouse liver.
Publication Title
Sexually dimorphic genome-wide binding of retinoid X receptor alpha (RXRα) determines male-female differences in the expression of hepatic lipid processing genes in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We performed microarray analysis in order to evaluate the combination effect of the mitochondrial matrix chaperone inhibitor gamitrinib-triphenylphosphonium (G-TPP) and Liver X receptor agonist LXR623 on gene expression in stem cell like glioma cells (NCH644).
Publication Title
Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples