PHLDA3 Impedes Somatic Cell Reprogramming Though Activating GSK3?

Embryonic stem cells(ESCs)are derived from the inner cell mass of a blastocyst.These cells hold the capacity of differentiating into various types ofcells,and are able to maintain their own undifferentiated state.Embryonic stem cells hold great promise in clinical therapy.People are now able to control the direction of embryonic stem cells differentiation and obtain specific cell types derived from ESCs.These new techniques give rise to new hope in regenerative medicine.However,there are certain concern and restrains when it comes to ESC clinical therapy.The resource of human ESCs are quite limited,and using human embryos to obtain ESCs may raise ethical concerns.iPS induction allows people to obtain ESC-like pluripotent stem cells derived from somatic cells.The technique of somatic cell reprogramming solves the problems of ESC clinical therapy.Also,this technique shows that terminally differentiated mammalian cells can also obtain pluripotency under certain circumstances for the first time.The efficiency of somatic cell reprogramming is extremely low,suggesting multiple barriers exist during this process.Increasing evidences have shown that p53 and its target genes play important roles in somatic cell reprogramming.In this study,we report that PHLDA3,a p53 target gene,functions as a blockage of iPS generation by activating the AKT-GSK3? pathway.Furthermore,PHLDA3 is found to be transcriptionally regulated by Oct4.These findings reveal that PHLDA3 acts as a new member of the regulatory network of somatic cell reprogramming.