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DNA methylation regulates lineage-specifying genes in the human vascular system.

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE32709: DNA methylation regulates lineage-specifying genes in the human vascular system [expression array]. GSE34486: DNA methylation regulates lineage-specifying genes in the human vascular system [methylation array]. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Silvia Rueberg

PROVIDER: E-GEOD-34487 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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DNA methylation regulates lineage-specifying genes in primary lymphatic and blood endothelial cells.

Brönneke Simone S Brückner Bodo B Peters Nils N Bosch Thomas C G TC Stäb Franz F Wenck Horst H Hagemann Sabine S Winnefeld Marc M

Angiogenesis 20120321 2

During embryonic development, the lymphatic system emerges by transdifferentiation from the cardinal vein. Although lymphatic and blood vasculature share a close molecular and developmental relationship, they display distinct features and functions. However, even after terminal differentiation, transitions between blood endothelial cells (BEC) and lymphatic endothelial cells (LEC) have been reported. Since phenotypic plasticity and cellular differentiation processes frequently involve epigenetic ...[more]

PMID: 22434260

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DNA methylation regulates lineage-specifying genes in the human vascular system [methylation array].

Project description:During embryonic development, the lymphatic system emerges by transdifferentiation from the cardinal vein. Although lymphatic and blood vasculature share a close molecular and developmental relationship, they display distinct features and functions. However, even after terminal differentiation, transitions between the two endothelial cell types have been reported. Since changes in phenotypic plasticity and cellular differentiation processes frequently involve epigenetic mechanisms, we wondered whether DNA methylation might play a role in regulating cell type-specific expression in endothelial cells. By analyzing global gene expression and methylation patterns of primary human dermal lymphatic and blood endothelial cells, we identified a highly significant set of genes, which were differentially methylated and expressed. Pathway analyses of the differentially methylated and upregulated genes in lymphatic endothelial cells revealed involvement in developmental and transdifferentiation processes. We further identified a set of novel genes, which might be implicated in regulating BEC-LEC plasticity and could serve as therapeutic targets and/or biomarkers in vascular diseases associated with alterations in the endothelial phenotype. Bisulphite converted DNA from the 16 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.1

2012-04-09 | E-GEOD-34486 | biostudies-arrayexpress

DNA methylation regulates lineage-specifying genes in the human vascular system [expression array].

Project description:During embryonic development, the lymphatic system emerges by transdifferentiation from the cardinal vein. Although lymphatic and blood vasculature share a close molecular and developmental relationship, they display distinct features and functions. However, even after terminal differentiation, transitions between the two endothelial cell types have been reported. Since changes in phenotypic plasticity and cellular differentiation processes frequently involve epigenetic mechanisms, we wondered whether DNA methylation might play a role in regulating cell type-specific expression in endothelial cells. By analyzing global gene expression and methylation patterns of primary human dermal lymphatic and blood endothelial cells, we identified a highly significant set of genes, which were differentially methylated and expressed. Pathway analyses of the differentially methylated and upregulated genes in lymphatic endothelial cells revealed involvement in developmental and transdifferentiation processes. We further identified a set of novel genes, which might be implicated in regulating BEC-LEC plasticity and could serve as therapeutic targets and/or biomarkers in vascular diseases associated with alterations in the endothelial phenotype. Expression profile of 10 lymphatic endothelial cells was compared to that of 6 blood endothelial cells, no replicates, no control samples.

2012-04-09 | E-GEOD-32709 | biostudies-arrayexpress

ncRNA (non-coding RNA) signature in endothelial cells during hypoxia [RNA-seq]

Project description:To define ncRNA expression in hypoxic endothelial cells, we applied pro-angiogenic hypoxia to cultured endothelial cells. Afterwards, total RNA was isolated and underwent RNA-seq analysis. HUVECs were subjected to normoxic or hypoxic (0.1-0.2% O2) cell culture conditions.

2015-07-01 | E-GEOD-70330 | biostudies-arrayexpress

ncRNA (non-coding RNA) signature in endothelial cells during hypoxia

Project description:To define ncRNA expression in hypoxic endothelial cells, we applied pro-angiogenic hypoxia to cultured endothelial cells. Afterwards total RNA was isolated and underwent genechip analysis. HUVECs were subjected to normoxic or hypoxic (0.1-0.2% O2) cell culture conditions.

2015-06-25 | E-GEOD-70034 | biostudies-arrayexpress

Deciphering early phosphoproteome changes in response to BMP9 and BMP10 in endothelial cells

Project description:BMP9 and BMP10 are two key regulators of vascular homeostasis. These two ligands bind with high affinity to the endothelial type I receptor ALK1 together with a type 2 receptor. Mutations in this signaling pathway have been identified in two rare cardiovascular diseases, hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension. So far, only the canonical SMAD signaling pathway has been extensively studied in response to BMPs. The aim of this work was to address early phosphoproteomic changes in endothelial cells in response to short-term stimulation (30 mins) with BMP9 and BMP10 in order to identify new phosphorylated targets and signaling pathways.

2024-03-25 | PXD044952 | Pride

Identification of common endothelial intronic circular RNAs from different vascular beds

Project description:The study aimed to identify circular RNAs (circRNAs) commonly back-spliced to intronic region of different sets of endothelial cells (human cardiac microvascular endothelial cells (HCMEC), human aortic endothelial cells (HAoEC), human umbilical vein endothelial cells (HUVECs)) and to evaluate their overall expression and their expression compared to their respective host gene. Identified circRNAs were quality controlled by their detection in an additional exonuclease RNase R treated RNA-Seq dataset performed with RNA of HUVECs. CircRNAs were compared for overlapping detection between datasets and filtered by annotation for circRNAs back-spliced to intronic regions. Common endothelial intronic circRNAs candidates were compared to respective murine circRNAs stored in the circATLAS database. The prime candidate cZNF292 was functionally characterized in vivo and in vitro.

2023-11-30 | E-MTAB-11171 | biostudies-arrayexpress

Transcription profiling of human pulmonary valve endothelial cells treated in culture by VEGF and VEGF+CsA

Project description:Transcription profiling of human pulmonary valve endothelial cells treated in culture by VEGF and VEGF+CsA

2010-08-17 | E-TABM-765 | biostudies-arrayexpress

Breast cancer endothelial interaction

Project description:MATERIALS AND METHODS: The genomic effects of tumor-endothelial interactions in cancer are not yet well characterized. To study this interaction in breast cancer, we set up an ex vivo coculture model with human benign and malignant breast epithelial cells with endothelial cells to determine the associated gene expression changes using DNA microarrays. RESULTS: The most prominent response to coculture was the induction of the M-phase cell cycle genes in a subset of breast cancer cocultures that were absent in cocultures with normal breast epithelial cells. In monoculture, tumor cells that contained the stem cell-like CD44(+)/CD24(-) signature had a lower expression of the M-phase cell cycle genes than the CD44(-)/CD24(+) cells, and in the CD44(+)/CD24(-) cocultures, these genes were induced. Pretreatment gene expression profiles of early-stage breast cancers allowed evaluating in vitro effects in vivo. The expression of the gene set derived from the coculture provided a basis for the segregation of the tumors into two groups. In a univariate analysis, early-stage tumors with high expression levels (n = 137) of the M-phase cell cycle genes had a significantly lower metastasis-free survival rate (P = 1.8e - 5, 50% at 10 years) and overall survival rate (P = 5e - 9, 52% at 10 years) than tumors with low expression (n = 158; metastasis-free survival, 73%; overall survival, 84%). CONCLUSIONS: Our results suggest that the interaction of endothelial cells with tumor cells that express the CD44(+)/CD24(-) signature, which indicates a low proliferative potential, might explain the unexpected and paradoxical association of the CD44(+)/CD24(-) signature with highly proliferative tumors that have an unfavorable prognosis. Computed

2010-02-17 | E-GEOD-20364 | biostudies-arrayexpress

PDGFR-alpha inhibits melanoma growth via CXCL10/IP-10 and miR-503. A multi-omics approach.

Project description:Cutaneous melanoma is the most aggressive skin cancer showing high mortality at advanced clinical stages. Platelet-Derived Growth Factor Receptor alpha (PDGFR-alpha) is known to strongly inhibit melanoma and endothelial cells proliferation, in vitro as well in vivo. PDGFR-alpha expression has been found to be reduced in metastatic human melanoma-biopsies, as compared to benign nevi-biopsies, thus implying a negative selection of PDGFR-alpha expressing cells, in melanoma. In the present study PDGFR-alpha was transiently overexpressed in endothelial (HUVEC) and melanoma (SK-Mel-28) human cells; a strong anti-proliferation effect was observed, along with profound effects on mRNA and miRNA expression. In detail, gene-expression profiling showed that PDGFR-alpha over-expression affects the expression of 82 transcripts in HUVEC (41 up-, 41 down-regulated), and 52 Transcripts in SK-Mel-28 (43 up-, 9 down-regulated). Finally, a miRNA profiling showed that 14 miRs are up-regulated and 39 are down-regulated in PDGFR-alpha overexpressing cells. Accurate validation with alternative techniques demonstrated that CXCL10 is one of the most significantly up-regulated at both gene- and protein level, in combination with a strong down-regulation of miR-503 in both HUVEC and SK-Mel-28 overexpressing PDGFR-alpha. We then demonstrate that CXCL10 is a validated miR-503 target, and that the anti-proliferation effect of PDGFR-alpha is reverted by specific CXCL-10 neutralization. In conclusion, PDGFR-alpha overexpression strongly inhibits endothelial- and melanoma- proliferation in a CXCL-10 dependent way, by significantly down-regulating miR-503 expression. This data set contains the results of the mRNA analysis.

2016-11-14 | E-MTAB-4261 | biostudies-arrayexpress

Transcription profiling of human gastric cancer endothelial cells and normal tissue endothelial cells

Project description:Identification of genes differentially expressed in gastric cancer endothelial cells compared to normal tissue endothelial cells.

2009-02-04 | E-TABM-424 | biostudies-arrayexpress

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