Bioinformatic identification and characterization of human endothelial cell-restricted genes

Hasan H Otu,Towia A Libermann,Lei Yuan,Peter Oettgen,Derin B Keskin,Manoj Bhasin

doi:10.1186/1471-2164-11-342

Hasan H Otu, Towia A Libermann + Show 4 more

Open Access

https://doi.org/10.1186/1471-2164-11-342

Copy DOI

Abstract

BackgroundIn this study, we used a systematic bioinformatics analysis approach to elucidate genes that exhibit an endothelial cell (EC) restricted expression pattern, and began to define their regulation, tissue distribution, and potential biological role.ResultsUsing a high throughput microarray platform, a primary set of 1,191 transcripts that are enriched in different primary ECs compared to non-ECs was identified (LCB >3, FDR <2%). Further refinement of this initial subset of transcripts, using published data, yielded 152 transcripts (representing 109 genes) with different degrees of EC-specificity. Several interesting patterns emerged among these genes: some were expressed in all ECs and several were restricted to microvascular ECs. Pathway analysis and gene ontology demonstrated that several of the identified genes are known to be involved in vasculature development, angiogenesis, and endothelial function (P < 0.01). These genes are enriched in cardiovascular diseases, hemorrhage and ischemia gene sets (P < 0.001). Most of the identified genes are ubiquitously expressed in many different tissues. Analysis of the proximal promoter revealed the enrichment of conserved binding sites for 26 different transcription factors and analysis of the untranslated regions suggests that a subset of the EC-restricted genes are targets of 15 microRNAs. While many of the identified genes are known for their regulatory role in ECs, we have also identified several novel EC-restricted genes, the function of which have yet to be fully defined.ConclusionThe study provides an initial catalogue of EC-restricted genes most of which are ubiquitously expressed in different endothelial cells.

Highlights

In this study, we used a systematic bioinformatics analysis approach to elucidate genes that exhibit an endothelial cell (EC) restricted expression pattern, and began to define their regulation, tissue distribution, and potential biological role
Identification of EC-restricted genes In an effort to identify genes that exhibit an ECrestricted pattern total RNA was isolated from primary cultured ECs and non-ECs (HASMC, B cells, T cells)
The cladogram produced by unsupervised clustering depicted that venous and pulmonary arterial ECs are much closer in expression profile as compared to microvascular cells

Summary

Introduction

We used a systematic bioinformatics analysis approach to elucidate genes that exhibit an endothelial cell (EC) restricted expression pattern, and began to define their regulation, tissue distribution, and potential biological role. The endothelium plays an important role in several human diseases. There are significant differences in EC structure and function based on the size and type of blood vessel, from larger arteries or veins, to medium sized arterioles or venules, down to capillary ECs. There is significant heterogeneity at the level of a particular tissue or organ. In the brain, the endothelium plays a important protective role as part of the blood brain barrier with ECs that are closely attached to one another forming a tight barrier that is impermeable to the passage of even small solutes or ions. In the liver, the sinusoidal ECs are fenestrated so that small to moderate size transcellular pores promote the uptake of large lipid containing particles from the blood [3,4]

Objectives

Methods

Results

Discussion

Conclusion