Constitutively active SMAD2/3 facilitates efficient transcription factor-mediated cell conversion

The generation of induced pluripotent stem cells (iPSCs) is a promising and exciting tool for regenerative medicine. Since their first appearance in 2006 by Yamanaka et al, where adult mouse fibroblasts were reprogrammed using a cocktail of only four master transcription factors (TFs), Oct4, Sox2, Klf4, and c-Myc reprogramming factors (1), iPSCs have served as valuable tools in studying disease. Indeed, even years after this groundbreaking discovery, cellular identity conversion of somatic cells through exogenous introduction of TFs towards iPSCs remains one of the most powerful tools (2) for disease modelling, drug screening, tissue engineering and transplantation therapies. Nevertheless, despite recent advances, the induction efficiency of these cells and subsequent differentiation to the desired cell types is, very low (3) and has a lengthy reprogramming process with substantial limitations to create and maintain functional cells. In a combined effort, laboratories led by Keisuke Kaji investigated a new approach of improving the efficiency of iPSCs generation by the reprogramming factors through the expression of constitutively active SMAD2/3 (4).