DNp73 improves generation efficiency of human induced pluripotent stem cells

Transcription factors, Oct4, Sox2, Klf4 and cMyc (4TF, Yamanaka factors) are used as basal conditions to generate iPS cells. In addition, the factor of DNp73(actually alpha splicing DNp73, DNp73α) is used to generate iPS cells. The experiment found that the addition of DNp73 gene increases human iPS cell generation efficiency by 12.6 folds in comparison to human fibroblast cells transduced with only the basal conditions. Also, iPS cells generated with DNp73 expression are more resistant to in vitro and in vivo differentiation.This study found DNp73, a family member of p53, is also involved in the human iPS cell generation. Specifically, that the involvement of DNp73 generates iPS cells that are more resistant to in vitro and in vivo differentiation. Therefore, this data may prove to be useful in future developmental studies and cancer researches.Human induced pluripotent stem cells hold great promise in regenerative medicine, disease modeling, and drug discovery [1,2]. However, the iPS cell generation efficiency is extremely low at around 1 from 10,000 parental cells [1,2], limiting its' use. Also, such a low efficiency suggests that major factors in de-differentiation or reprogramming have not been identified yet. Recently, a series of breakthrough discoveries have brought to attention that, blocking the important tumor suppressor protein p53, and its downstream pathways, dramatically improves generation efficiency of induced pluripotent stem cells [3-7]. The data suggest that p53 is a key link between cellular reprogramming and tumor formation since it prevents differentiated cells from transforming into pluripotent stem cells.In 2005, we found that p53 induced differentiation of mouse embryonic stem (ES) cells by inhibiting a core transcription factor, Nanog, in the presence of stresses [8]. Nanog is a key ES cell transcription factor; Loss of Nanog expression led to rapid differentiation [9,10]. The p53 protein directly binds to the Nanog promoter to suppress it