Abstract

The placenta serves to bring the maternal and fetal circulatory systems into close proximity to allow efficient transfer of oxygen, nutrients and waste products. This requires profound and substantial growth and remodeling of blood vessels. These processes are sensitive to changes in the local placental environment and can be disturbed under pathological conditions leading to aberrant vessel architecture and compromise of placental function. The coordination of appropriate and well-ordered growth depends on the complex integration of numerous contact and soluble factor-mediated signals. Endothelial behavior ultimately depends on the cellular genome and this can be interrogated by investigating changes in the transcript profile under differing conditions. We have sought to define “regulatory gene networks” in endothelial cells to further our understanding endothelial cell and hence, placental function. To do this we have analyzed the endothelial transcript profile after knocking down approximately 400 different transcripts. Using Bayesian statistical methods, we have modeled the transcript regulatory network. This has shown that there is a relatively small number of “hub-like” genes that play a key role in regulating endothelial cell fate. The array data is a substantial resource that will be useful in unraveling endothelial behavior under a range of differing stimuli.