Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Decidual Endothelial Cells (DEC) and endothelial cells from human skin (ADMEC)

ABSTRACT: BACKGROUND: endothelial cells (ECs) form a continuous barrier between blood and tissues and gate the traffic of molecules and cells across the vessel wall playing an active role in hemostasis, inflammation and immunity. Decidual endothelial cells (DECs) are located in a very special district from the immunological and inflammatory point of view since decidua has immunoregulatory and pro-angiogenic functions. The aim of this study was to compare the phenotype of microvascular ECs isolated from decidua with microvascular ECs isolated from other vascular districts. METHOD: we analyzed the differences in molecules involved in angiogenesis and leukocyte recruitment between DECs and endothelial cells from human skin (ADMECs) which are normally involved in inflammatory response by microarray analysis. RESULTS: our results showed that DECs are able to produce high amount of the growth factors HGF, VEGF-A and IGFBP3, important for the control of angiogenesis and express the adhesion molecules ICAM2 and ICAM3 in basal condition, important molecules for the control of leukocyte recruitment and function. We demonstrated also that DECs do not up-regulate the expression of ICAM1 in response to pro-inflammatory cytokines and produce high amount of the chemokines CXCL9/MIG and CXCL10/IP-10 in response to IFN-a. CONCLUSION: we conclude that the phenotype of these cells strongly differs from that of other endothelial cells such as ADMECs which have to be quickly able to response to infections and other pro-inflammatory stimuli. These data suggest that endothelial cells may play an active in the control of local immune response at foeto-maternal interface. Single color gene expression in human endothelial cells. Six independent experiments (3 DEC vs 3 ADMEC) were performed using different donors for each experiment.

ORGANISM(S): Homo sapiens

SUBMITTER: Riccardo Bomben

PROVIDER: E-GEOD-41946 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Although differentiation of mice embryonic stem cells into vascular endothelial cells (ECs) gives a model for investigating molecular mechanisms of vascular development in vivo, temporal dynamics of gene expressions and chromatin modifications have not been studied until now. Here, we interrogated transcriptome and two histone modifications, H3K4me3 and H3K27me3, with a genome-wide scale during ECs differentiation and elucidated epigenetic switch peculiar to ECs. We find Gata2, Fli1, Sox7, and Sox18 are master regulators from genetic and epigenetic data, these genes were induced after Etv2 activation. These genes have specific histone modification pattern which is repressed by H3K27me3 modification at Flk-sorted mesoderm and changed to the bivalent (H3K4me3 and H3K27me3 both positive) state rapidly after vascular endothelial cells growth factor (VEGF) stimuli. Using a previously reported ECs differentiation model, we demonstrate that four transcription factors are critical for ECs specific gene expressions and efficient differentiation. Moreover, from knockdown experiments using si-RNA, we discovered these factors inhibited not only TGFÎ² signaling pathway, that is endothelial mesenchymal transition pathway, but also other near lineage commitment, including blood cells, skeletal muscle cells, vascular smooth muscle cells, and cardiomyocytes. We further identify each factor specific target genes during ECs differentiation by microarray, including both activating and repressing genes. Together, our findings from a detailed epigenetic approach provide a basic understanding temporal regulated chromatin signatures and resulting gene expression profile during ECs commitment, which is applicable to other models of differentiation and production of mature and long lasting ECs for regenerative medicine. Total 17 samples were derived from [1] ES cells, Flk-sorted mesoderm cells, and in the absense or presence of VEGF (6, 12, 24, and 48h) to determine VEGF activated genes during endothelial cells differentiation, [2] control si-RNA, si-Gata2, si-Fli1, si-Sox7, or si-Sox18 transfected cells under VEGF stimuli, [3] control si-RNA or si-Mix (si-Gata2, si-Fli1, si-Sox7, and si-Sox18) transfected cells under VEGF stimuli for the identification of each transcription factor dependent genes during endothelial cells differentiation.

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Decidual Endothelial Cells (DEC) and endothelial cells from human skin (ADMEC)

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