Microarray analysis of trophoblast differentiation: gene expression reprogramming in key gene function categories

Placental development results from a highly dynamic differentiation program . We used DNA microarray analysis to characterize the process by which huma n cytotrophoblast cells differentiate into syncytiotrophoblast cells in a p urified cell culture system. Of 6,918 genes analyzed, 141 genes were induce d and 256 were downregulated by more than 2-fold. Dynamically regulated gen es were divided by the K-means algorithm into 9 kinetic pattern groups, the n by biologic classification into 6 overall functional categories: cell and tissue structural dynamics, cell cycle and apoptosis, intercellular commun ication, metabolism, regulation of gene expression, and expressed sequence tag (EST) and function unknown. Gene expression changes within key function al categories were tightly coupled to morphological changes. In several key gene function categories, such as cell and tissue structure, many gene mem bers of the category were strongly activated while others were strongly rep ressed. These findings suggest that differentiation is augmented by "catego rical reprogramming" in which the function of induced genes is enhanced by preventing the further synthesis of categorically related gene products.