Denunded HUVEC/HUASMC spheroids vs. HUASMC spheroids
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156274 | GEO | 2020/12/17
REPOSITORIES: GEO
Similar Datasets
Project description:Smith-Lemli-Opitz syndrome is an autosomal recessive disorder that arises from mutations in the gene DHCR7, which encodes the terminal enzyme of cholesterol biosynthesis, leading to decreased production of cholesterol and accumulation of the cholesterol precursor, 7-dehydrocholesterol, and its oxysterol metabolites. The disorder displays a wide range of neurodevelopmental defects, intellectual disability and behavioral problems. However, an in-depth study on the temporal changes of gene expression in the developing brains of SLOS mice has not been done before. In this work, we carried out the transcriptomic analysis of whole brains from WT and Dhcr7-KO mice at four time points through postnatal day 0. First, we observed the expected downregulation of the Dhcr7 gene in the Dhcr7-KO mouse model, as well as gene expression changes of several other genes involved in cholesterol biosynthesis throughout all time points. Pathway and GO term enrichment analyses revealed affected signaling pathways and biological processes that were shared amongst time points and unique to individual time points. Specifically, the pathways important for embryonic development, including Hippo, Wnt, and TGF-β signaling pathways are the most significantly affected at the earliest time point, E12.5. Additionally, neurogenesis-related GO terms were enriched in earlier time points, consistent with the timing of development. Conversely, pathways related to synaptogenesis, which occurs later in development compared to neurogenesis, are significantly affected at the later time points, E16.5 and PND0, including the cholinergic, glutamatergic, and GABAergic synapses. The impact of these transcriptomic changes and enriched pathways is discussed in the context of known biological phenotypes of SLOS.
2024-02-15 | GSE247566 | GEO
Project description:7-dehydrocholesterol reductase catalyzes the reduction of 7-dehydrocholesterol to cholesterol. In Smith-Lemli-Opitz syndrome, mutations in DHCR7 prevents this conversion. We have found iPS cells derived from SLOS patients exhibit accelerated differentiation under cholesterol poor conditions. In this dataset, we include expression data obtained from comparision of a control iPS cell line (BJ) and a SLOS iPS cell line (A2). Cell line gene expression was compared in cholesterol rich conditions where the SLOS phenotype is suppressed. Cholesterol deficient culture of control and SLOS iPS cells demonstrated enhanced differentiation of SLOS cells over 7 days. These data are used to obtain 308 genes that are differentially expressed upon cholesterol deficient culture. time-course expression data obtained from control and SLOS patient iPS cells after transfer from cholesterol rich to cholesterol deficient culture.
2015-09-18 | GSE61203 | GEO
Project description:The genetic defect underlying the human Smith-Lemli-Opitz dysmorphological disorder is loss-of-function mutations affecting the cholesterol synthesis enzyme dehydrocholesterol delta7 reductase, DHCR7. Dhcr7 knockout mice recapitulate the biochemical characteristics, but all knockout pups die within 14h of birth. Tissues of knockout mice accumulate the precursor sterol, 7-dehydrocholesterol, and show reduced levels of cholesterol (J. Clin. Invest. (2001) 108: 905-915). We compared the global gene expression changes in lung, liver and brain from knockout mice to those seen from organs harvested from same-pregnancy wild-type embryos, harvested before birth (E18.5). Since the P0 knockout pups die, we expected that there would be significant changes in gene expression between knockout and wild-type organs, and further comparing the altered genes in common to brain, lung and liver would point to a common mechanistic pathway where disruption of normal sterol synthesis in all cells leads to pathophysiology. Remarkably, these data show that the global gene expression between knockout and wild-type organs is hardly altered, despite the complete loss of cholesterol synthesis. There are so few genes that are altered, and furthermore, those that are altered are very limited in sharing similarities in all three tissues. This suggests that disorganized gene expression is not the cause of the early neonatal lethality. Dhcr7+/- females were mated with Dhcr+/- males, and timed pregnancy obtained. At E18.5, pregnant dams were sacrificed, and embryos harvested, organs removed and RNA extracted, and all embryos were genotyped. Matching wild-type and knockout embryos were taken from each pregnancy, and two females yielded all genotypes used herein.
2012-08-01 | E-GEOD-39811 | biostudies-arrayexpress
Project description:The response of primary human endothelial (ECs) and vascular smooth muscle cells (VSMCs) to TiO2 nanotube arrays is studied through gene expression analysis. Microarrays revealed that nanotubes enhanced EC proliferation and motility, decreased VSMC proliferation, and decreased expression of molecules involved in inflammation and coagulation in both cell types. Network generated from significantly affected genes suggests that cells may be sensing nanotopographical cues via pathways previously implicated in sensing shear stress. DNA microarrays were used to analyze the response of primary human endothelial (ECs) and vascular smooth muscle cells (VSMCs) to nanotopographical TiO2 surfaces. The experiment incorporated a 1 color design and used Agilent arrays that contained roughly 44,00 60mer probes that provide complete coverage of the human genome. 19 arrays were hybridized and represent 4 biological replicates for each group ( with the exception of group VSMC-NT30, which has 3 biological replicates). Data was analyzed separately for each cell type ( EC or VSMC). Gene expression comparisons were made between control cells grown on flat titanium (Ti) and cells grown on either 30nm nanotubes (NT30) or 100nm nantubes ( NT-100).
2010-08-14 | E-GEOD-17676 | biostudies-arrayexpress
Project description:Feeding animals with either concentrates or alfalfa grazing has been proven to reduce the oxidative process that occurs in meat products. Indoor-kept lambs were fed a standard concentrate (n=7, C) before slaughtering all animals at 22–24 kg of live weight. Simultaneously, 7 unweaned lambs grazed in alfalfa paddocks (ALF) with their dams. Global transcriptomic data of liver with the Affymetrix® Ovine Gene 1.1 microarray was used. When ALF group was compared with C group, were identified 96 genes differentially expressed. Among these genes 92 were down- regulated and 4 were up- regulated. The clusters corresponding to gene expression profiles from treatments were clearly separated from each other. These differentially expressed genes were selected for a functional analysis by using DAVID. Three major gene clusters associated with “sterol biosynthesis (EBP, MVD, HMGCR, CYP51A1, HMGCS1, NR0B2, C14ORF1, FDFT1, SQLE, DHCR7, SC5DL, DHCR24, NSDHL) , “lipid biosynthetic process (ACACA, CYP51A1, FADS1, FADS2, SCD y SC5DL)”, “cholesterol metabolic process (EBP, MVD, HMGCR, CYP51A1, SQLE, DHCR7, HMGCS1, NR0B2, DHCR24, FDFT1, NSDHL)” were found.
2019-02-05 | GSE125661 | GEO
Project description:Although oncogenicity of the stem cell regulator SOX9 has been implicated in many solid tumors, its role in lymphomagenesis remains largely unknown. In this study, we showed that SOX9 is overexpressed preferentially in a subset of diffuse large B-cell lymphomas (DLBCL) harboring IGH-BCL2 translocations. SOX9 positivity in DLBCL correlates with advanced stage of disease. Silencing of SOX9 decreased cell proliferation, induced G1/S arrest and increased apoptosis of DLBCL cells, both in vitro and in vivo. Whole transcriptome analysis and CHIP-seq assays identified DHCR24, a terminal enzyme in cholesterol biosynthesis, as a direct target of SOX9, which promotes cholesterol synthesis by increasing DHCR24 expression. Enforced expression of DHCR24 was capable of rescuing the phenotypes associated with SOX9 knockdown in DLBCL cells. In DLBCL cell line xenograft models, SOX9 knockdown resulted in lower DHCR24 level, reduced cholesterol content and decreased tumor load. Pharmacological inhibition of cholesterol synthesis also inhibited DLBCL xenograft tumorigenesis, the reduction of which is more pronounced in DLBCL cell line with higher SOX9 expression, suggesting that it may be addicted to cholesterol. In summary, our study demonstrates that SOX9 can drive lymphomagenesis through DHCR24 and the cholesterol biosynthesis pathway. This SOX9-DHCR24-cholesterol 3 biosynthesis axis may serve as a novel treatment target for DLBCL.
2022-01-12 | GSE180051 | GEO
Project description:Although oncogenicity of the stem cell regulator SOX9 has been implicated in many solid tumors, its role in lymphomagenesis remains largely unknown. In this study, we showed that SOX9 is overexpressed preferentially in a subset of diffuse large B-cell lymphomas (DLBCL) harboring IGH-BCL2 translocations. SOX9 positivity in DLBCL correlates with advanced stage of disease. Silencing of SOX9 decreased cell proliferation, induced G1/S arrest and increased apoptosis of DLBCL cells, both in vitro and in vivo. Whole transcriptome analysis and CHIP-seq assays identified DHCR24, a terminal enzyme in cholesterol biosynthesis, as a direct target of SOX9, which promotes cholesterol synthesis by increasing DHCR24 expression. Enforced expression of DHCR24 was capable of rescuing the phenotypes associated with SOX9 knockdown in DLBCL cells. In DLBCL cell line xenograft models, SOX9 knockdown resulted in lower DHCR24 level, reduced cholesterol content and decreased tumor load. Pharmacological inhibition of cholesterol synthesis also inhibited DLBCL xenograft tumorigenesis, the reduction of which is more pronounced in DLBCL cell line with higher SOX9 expression, suggesting that it may be addicted to cholesterol. In summary, our study demonstrates that SOX9 can drive lymphomagenesis through DHCR24 and the cholesterol biosynthesis pathway. This SOX9-DHCR24-cholesterol 3 biosynthesis axis may serve as a novel treatment target for DLBCL.
2022-01-12 | GSE179960 | GEO
Project description:The genetic defect underlying the human Smith-Lemli-Opitz dysmorphological disorder is loss-of-function mutations affecting the cholesterol synthesis enzyme dehydrocholesterol delta7 reductase, DHCR7. Dhcr7 knockout mice recapitulate the biochemical characteristics, but all knockout pups die within 14h of birth. Tissues of knockout mice accumulate the precursor sterol, 7-dehydrocholesterol, and show reduced levels of cholesterol (J. Clin. Invest. (2001) 108: 905-915). We compared the global gene expression changes in lung, liver and brain from knockout mice to those seen from organs harvested from same-pregnancy wild-type embryos, harvested before birth (E18.5). Since the P0 knockout pups die, we expected that there would be significant changes in gene expression between knockout and wild-type organs, and further comparing the altered genes in common to brain, lung and liver would point to a common mechanistic pathway where disruption of normal sterol synthesis in all cells leads to pathophysiology. Remarkably, these data show that the global gene expression between knockout and wild-type organs is hardly altered, despite the complete loss of cholesterol synthesis. There are so few genes that are altered, and furthermore, those that are altered are very limited in sharing similarities in all three tissues. This suggests that disorganized gene expression is not the cause of the early neonatal lethality.
2012-08-02 | GSE39811 | GEO
Project description:7-dehydrocholesterol reductase catalyzes the reduction of 7-dehydrocholesterol to cholesterol. In Smith-Lemli-Opitz syndrome, mutations in DHCR7 prevents this conversion. We have found iPS cells derived from SLOS patients exhibit accelerated differentiation under cholesterol poor conditions. In this dataset, we include expression data obtained from comparision of a control iPS cell line (BJ) and a SLOS iPS cell line (A2). Cell line gene expression was compared in cholesterol rich conditions where the SLOS phenotype is suppressed. Cholesterol deficient culture of control and SLOS iPS cells demonstrated enhanced differentiation of SLOS cells over 7 days. These data are used to obtain 308 genes that are differentially expressed upon cholesterol deficient culture. time-course expression data obtained from control and SLOS patient iPS cells after transfer from cholesterol rich to cholesterol deficient culture. 48 total RNA samples were isolated and hybridized on Affymetrix arrays. We generated the following pairwise comparisons using Partek: BJ 0hr vs A2 0hr; BJ 2Day vs A2 2Day; BJ 3Day vs A2 3Day; BJ 4Day vs A2 4Day; BJ 5Day vs A2 5Day; BJ 7Day vs A2 7Day. Genes with an FDR≤10% and a fold-change ≥3 were identified as significantly different. We also performed pairwise comparison of BJ and A2 samples within each cell line between subsequent isolations (i.e. BJ 0hr vs BJ 2Day; A2 3Day vs A2 4Day; etc.)
2015-09-18 | E-GEOD-61203 | biostudies-arrayexpress
Project description:Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder caused by autosomal recessive mutations in the Dhcr7 gene. SLOS patients present clinically with multiple dysmorphologies, neurological, behavioral and cognitive defects, and demonstrate impaired cholesterol biosynthesis resulting in markedly elevated 7-DHC in all bodily tissues and fluids. Previous rodent models of SLOS suffered from neonatal mortality or variation in the biochemical phenotype over time. We generated a viable murine model bearing a conditional flosed allele of the Dhcr7 gene, and validated it by generating a mice with liver-specific deletion of Dhcr7 by breeding with a strain expressing Cre recombinase driven by an albumin promoter . These mice demonstrated elevated circulatory and liver 7-DHC levels, but phenotypic characterization of the knockout mice revealed no significant changes in viability, fertility, growth curves, liver architecture, hepatic triglyceride secretion, and parameters of systemic glucose homeostasis. Investigation in to changes in the liver transcriptome were investigated withe RNAseq, and identified enrichment in various pathways, including steroid hormone biosynthesis and various cell signaling and metabolism pathways. Most notably missing from the list are the genes related to cholesterol biosynthesis. Generation of this Dhcr7 conditional knockout model will allow for better studies into the post natal effects of blocking cholesterol biosynthesis, accumulation of 7-DHC, and the role of DHCR7 in specific tissues.
2020-09-04 | GSE146523 | GEO