Cell fates as attractors: Stability and flexibility of cellular phenotypes

The vascular endothelial cell (EC) is one of perhaps thousands of “cell types” in the body of higher vertebrates for which a definition as a distinct type is fairly straightforward. A vascular EC is naturally defined by its distinct anatomical and physiological attributes as the cell lining the blood vessels and in contact with circulating blood. In general, we do not yet have a handle for a precise, systematic, and comprehensive taxonomy for all the cell types in the body. Nevertheless, in molecular terms, it appears that a cell type can be characterized by its distinct transcriptome and proteome – that is, by a genome–scale combinatorial code of the expression status of tens of thousands of genes, akin to a very long bar code. Currently, DNA microarray-based gene expression profiling at the level of mRNA abundance and subsequent cluster analysis of the high-dimensional set of molecular attributes reveal highly robust expression profiles that can readily be grouped into similarity “clusters” that correspond to the individual tissues or cell types as defined by physiology and histology (1,2). Morphologically and at the molecular level, the EC cell type consists of an entire class of distinct subtypes defined by their location in the hierarchy of the vasculature (arteries, arterioles, capillaries, venules, and veins) as well as by tissue bed (e.g., brain versus dermal capillary ECs). In addition to this apparently static variation that is manifest as the stable subtypes, gene expression patterns in an EC also vary with the dynamics of functional states, such as the switching from a quiescent to “activated” state during inflammation, or to the proliferating and migrating state during angiogenesis.