Identification of key factors and molecular mechanism that determine proliferation-quiescence state by optogenetic approach

Abstract

Cell has a series of tightly regulated molecular events, called the cell cycle, to produce a two daughter cells from a single mother cell. Individual metazoan cells have a choice to determine their fate of two mutually reversible state in every cell cycle: continual proliferation or paused quiescence. The complex regulatory network for these two reversible states has been established for decades to define the mechanisms beyond tissue homeostasis, normal development, and incurrence of cancer. G1 phase cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors have been studied to define their roles in the decision of proliferation and quiescence. Due to the development of live-cell sensors displaying the heterogenous characteristics of the cell, recent studies have suggested the essential roles of the G1 phase molecules in the cell cycle phases of the mother cells. Due to the lack of the way to specifically modulate the G1 phase molecules with high temporal resolution, the crucial factors that decide proliferative or quiescent state for a cell have not been discovered yet. In this research, we suggest to apply an optogenetic approach with high-specificity, temporal resolution, and reversibility to find the “Key factor” that regulates proliferation-quiescence decision in the mother cells and the specific “Key” cell cycle phase of the mother cells where the “Key factor” plays the essential role on the decision of the daughter cells’ fate.