The core endothelial cell enriched transcriptome

Endothelial cells line the inside of all vessels and have a critical role in the regulation of hemostasis, inflammation, defense against blood borne pathogens, vascular tone, angiogenesis and the transport of molecules and nutrients to and from the blood stream. Endothelial cells from different vascular beds can vary in gene expression profile, but proteins critical for key endothelial functions tend to be expressed specifically in this cell type across vascular beds.

In this section we detail the predicted core endothelial transcriptome, highlighting genes classified as having predicted specificity in endothelial cells in multiple tissue types. Such genes could be useful general markers for endothelial cells across tissue beds, and are likely critical for endothelial specific functions. These genes are sub-divided into 3 categories, based on the number of tissues in which they were independently classified as endothelial cell enriched.

Endothelial cells were profiled in 15 of the tissues featured in the Tissue Cell section.

• 20 genes predicted as enriched in endothelial cells in 75-100 % tissues
• 43 genes predicted as enriched in endothelial cells in 50-75 % tissues
• 132 genes predicted as enriched in endothelial cells in 25-50 % tissues

Protein expression of genes enriched in endothelial cells across tissue types

An example of a protein with predicted enriched expression in endothelial cells in multiple tissue types is the well known endothelial marker Platelet And Endothelial Cell Adhesion Molecule 1 (PECAM1), the expression of which is largely concentrated at the junctions between adjacent cells. PECAM1 plays a critical role in the maintenance of endothelial barrier function.

PECAM1 - Colon
PECAM1
PECAM1 - Heart muscle
PECAM1
PECAM1 - Lung
PECAM1
PECAM1 - liver
PECAM1

Dysferlin (DYSF) also had predicted enriched expression in endothelial cells in multiple tissue types. This protein is a member of the ferlin family, members of which are primarily known for their role in the regulation of plasma membrane repair in muscle cells. However, loss of dysferlin in endothelial cells can inhibit normal adhesion and causes degradation of PECAM1, indication that it also has an important functional role in this cell type.

DYSF - Adipose visceral
DYSF
DYSF - Breast
DYSF
DYSF - Kidney
DYSF

Aquaporin 1 (AQP1) was also predicted to be endothelial enriched in multiple tissues. AQP1 is a widely expressed water channel, the physiological function of which has been most thoroughly characterized in the kidney. Whilst there is little evidence to indicate it has a critical role in endothelial cells related to its transporter capacity, it has been implicated as having a role in endothelial migration and angiogenesis.

AQP1 - Prostate
AQP1
AQP1 - Skeletal muscle
AQP1
AQP1 - Testis
AQP1

Genes with predicted specificity in endothelial cells in individual tissues

A summary table of all genes with predicted high enrichment in endothelial cells in profiled tissues is provided below. Identified genes are subdivided into 3 categories in each tissue, based on the difference between the enrichment score in endothelial cells, compared to the other cell types profiled (see Methods Summary page for details):

• Predicted specificity: ´Very high´ - Differential score vs. other profiled cell types within the tissue >0.35
• Predicted specificity: ´High´ - Differential score vs. other profiled cell types within the tissue >0.25
• Predicted specificity: ´Moderate´ - Differential score vs. other profiled cell types within the tissue >0.15

Table 1: Genes predicted to be enriched in endothelial cells by tissue type