One possible reason could be the mesenchymal-to-epithelial (MET) transition. MET is a crucial step in normal embryogenesis and early development. Accordingly, it also occurs in the reprogramming process, mimicking these developmental steps in vitro. During reprogramming, three steps can be distinguished, namely, initiation, maturation, and stabilization [52]. MET is mainly present in the initiation phase of fibroblast reprogramming which precedes the upregulation of pluripotency markers. In the beginning, first epithelial-associated genes like EPCAM (epithelial cell adhesion molecule) or epithelial junctional protein E-cadherin (CDH1) are induced. In addition, transcription factors which maintain the mesenchymal phenotype by directly repressing epithelial gene expression are themselves repressed. This facilitates the switch from the mesenchymal to the ectodermal germ layer gene expression [52]. Keratinocytes are of ectodermal origin so no MET has to be passed which could have positive effects on the reprogramming efficiency and speed.
