The Jeremiah Metzger lecture. The origin of fibroblasts and the terminality of epithelial differentiation.

For 142 years the fibroblast has lived a nomadian existence among the interstitial spaces of the metazoan body plan. The cell surface of fibroblasts lacks specific identifying markers and its parental lineage has been shrouded in mystery. Over the last 15 years much has changed. We know now that fibroblasts derive from non-motile epithelial or endothelial cells through a process called epithelial-mesenchymal transition (EMT). In this lecture I discuss the mechanisms of EMT producing fibroblasts, and the inevitable conclusion that epithelia and endothelia, rather than being terminally differentiated, are in a state of nuclear diapause and ready to change phenotype in response to the demands of tissue repair.