Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Endothelial cell profiles

ABSTRACT: Umbilical vein, lung microvascular, aortic and coronary artery endothelial cell profiles generated. Further characterization gained by comparison with other selected cell types.

ORGANISM(S): Homo sapiens

SUBMITTER: Jennifer King

PROVIDER: E-GEOD-515 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of endothelial cell genes by combined database mining and microarray analysis.

Ho Michael M Yang Eugene E Matcuk George G Deng David D Sampas Nick N Tsalenko Anya A Tabibiazar Raymond R Zhang Ying Y Chen Mary M Talbi Said S Ho Yen Dong YD Wang James J Tsao Philip S PS Ben-Dor Amir A Yakhini Zohar Z Bruhn Laurakay L Quertermous Thomas T

Physiological genomics 20030513 3

Vascular endothelial cells maintain the interface between the systemic circulation and soft tissues and mediate critical processes such as inflammation in a vascular bed-selective fashion. To expand our understanding of the genetic pathways that underlie these specific functions, we have focused on the identification of novel genes that are differentially expressed in all endothelial cells, as well as restricted groups of this cell type. Virtual subtraction was conducted employing gene expressio ...[more]

PMID: 12644598

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Project description:Endothelial cells (EC) lining arteries and veins have distinct molecular and functional signatures. The (epi)genetic regulatory mechanisms underlying this heterogeneity in human EC are incompletely understood. Using genome-wide microarray screening we established a specific fingerprint of freshly isolated arterial (HUAEC) and venous EC (HUVEC) from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions and pathways. Among the arterial genes were 8 transcription factors, including HEY2, a downstream target of Notch signaling and the current ‘golden standard’ pathway for arterial EC specification. Short-term culture of HUAEC or HUVEC abrogated differential gene expression resulting in a default state. Erasure of arterial gene expression was at least in part due to loss of canonical Notch activity and HEY2 expression. Notably, nCounter analysis revealed that restoring HEY2 expression or Delta-like 4 (Dll4)-induced Notch signaling in cultured HUVEC or HUAEC only partially reinstated the arterial EC gene signature while combined overexpression of the 8 transcription factors restored this fingerprint much more robustly. Each transcription factor had a different impact on gene regulation, with some stimulating only few and others boosting a large proportion of arterial genes. Interestingly, although there was some overlap and cross-regulation, the transcription factors largely complemented each other in regulating the arterial EC gene profile. Thus, our study showed that Notch signaling determines only part of the arterial EC signature and identified additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity To identify an arteriovenous (AV) fingerprint in human endothelial cells (EC) across different vascular beds, we used microarrays on RNA from 38 EC samples corresponding to 6 cultured human arterial-EC types (hepatic artery EC or HHAEC, N=3; aorta EC or HAEC, N=2; coronary artery EC or HCAEC, N=2; iliac artery EC or HIAEC, N=2; pulmonary artery EC or HPAEC, N=3; and umbilical artery EC or HUAEC-C, N=5), 4 cultured human venous-EC types (hepatic vein EC or HHVEC, N=3; iliac vein EC or HIVEC, N=3; pulmonary vein EC or HPVEC, N=2; and umbilical vein EC or HUVEC-C, N=5), freshly isolated HUAEC (HUAEC-F, N=4) and freshly isolated HUVEC (HUVEC-F, N=4). Due to the difficulty to obtain biopsies from healthy donors, we did not have access to freshly isolated aEC or vEC matched for all cultured EC types.

Dataset Information

Endothelial cell profiles

Publications

Identification of endothelial cell genes by combined database mining and microarray analysis.

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