Reprogramming Fibroblasts to Endothelial Cells

Lianghui Zhang, Asrar B Malik, Jalees Rehman

"These results show that a nucleus can promote the formation of a differentiated intestine cell and at the same time contain the genetic information necessary for the formation of all other types of differentiated somatic cell in a normal feeding tadpole. It is concluded that the differentiation of a cell cannot be dependent upon the incapacity of its nucleus to give rise to other types f differentiated cell." This is the concluding paragraph of Sir John Gurdon's seminal study published in 1962, in which he demonstrated that nuclei from differentiated intestinal epithelial cells could give rise to normal tadpoles following transfer into an enucleated recipient egg(1). Half a century later, Gurdon would receive the Nobel Prize together with Shinya Yamanaka, whose equally seminal work had shown that adult mouse fibroblasts could be reprogrammed to a fully pluripotent stem cell state(2), for their contributions to reprogramming differentiated cells. Unlike Gurdon's nuclear transfer approach, Yamanaka's method relied on the expression of the transcription factors Oct4, Sox2, c-Myc and Klf4 (also known as the "Yamanaka factors") in fibroblasts, which activated the cells' dormant embryonic pluripotency gene network and generated induced pluripotent stem cells (iPSCs). The iPSCs, in turn, could then be differentiated into a variety of desired cell types such as neurons, hepatocytes or cardiomyocytes.