Mechanism Study On P18 Regulation Of Mouse Somatic Cell Reprogramming

Somatic cell can be converted to pluripotent cells by ectopic expression of transcription activation factors. iPSCs have similar self-renewal and pluripotency ability like embryonic stem cells. The somatic cell reprogramming undergoes a series of changes in cell cycle, like accelerated cell cycle, extended S phase and loss of G1 checkpoint. However, it is unclear that how is the cell cycle pattern changed during reprogramming. Study the reprogramming mechanism from the angle of cell cycle regulation will extend our understanding on reprogramming and potentially facilitate the clinical development of iPSCs.p18 is a very conserved protein among many species. As a member of Ink 4 protein family, p18 negatively regulates the Gl/s transition. Other members of Ink4 family have been consider as the blocker of reprogramming, however, the role of p18 during reprogramming is still unclear, when we ectopic express p18 during reprogramming, the E2F transcription activity is inhibited and a series of genes involved in DNA synthesis and cell cycle regulation cannot function properly, resulting in reduced reprogramming efficiency. Mechanism studies indicate p18 inhibit reprogramming through interacts with his downstream targets Cdk 6 but not Cdk4.