Molecular Characterization of F8 Secreting Cell

Different endothelial cells share common features but also acquire organ specificity: for example the liver sinusoidal endothelial cells (LSECs) are major site of F8 secretion as compared to other endothelial cells. To decipher this specificity in LSECs and to understand the molecular mechanism of F8 synthesis and secretion, we have compared genome wide expression and epigenetic data of fetal LSECs (N=3) and non-liver endothelial cells (HCMEC, HPAEC, HPMEC and HUVEC; N=3), hepatocytes (N=3) and adult total blood (N=3). At a false discovery rate of <5% we found 4134 differentially methylated CpG sites and 663 differentially expressed probes (corresponding to 623 genes/loci) between LSECs and other endothelial cells. The loci were found by ingenuity pathway analysis (IPA) to be enriched in EIF2, eIF4, p7056K and mTOR signaling pathways together with LXR/RXR activation pathway. On the other hand, only 21 different loci and 152 CpGs were found to be statistically different (at <5% FDR) between hepatocytes and LSECs. According to IPA these were found enriched in interferon signaling, activation of IRF by cytosolic pattern recognition receptors and role of pattern recognition receptor in recognition of bacteria and viruses. Additionally, gene ontology analysis showed enrichment in GO-terms such as regulation of cellular metabolic process for LSECs vs. endothelial cells and blood vessel development, cell adhesion and regulation of cell migration for LSECs vs. hepatocytes. Moreover, in each of the GO sub categories of general coagulation (GO:0007596) and transcription factors (GO:003700) a small number of loci successfully differentially identify the LSECs from other endothelial cells. The above described results show specific molecular signature that characterize the F8 secreting cells and highlight specific cellular pathways associated with this process.