Bioinformatic identification and characterization of human endothelial cell-restricted genes.
BACKGROUND
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.


RESULTS
Using 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.


CONCLUSIONS
The study provides an initial catalogue of EC-restricted genes most of which are ubiquitously expressed in different endothelial cells.
Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Manoj
M
Bhasin
Lei
L
Yuan
Derin B
DB
Keskin
Hasan H
HH
Otu
Towia A
TA
Libermann
Peter
P
Oettgen
D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019295:Computational Biology; D004194:Disease / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005796:Genes; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D009928:Organ Specificity; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D035683:MicroRNAs; D014157:Transcription Factors