We are investigating molecular mechanisms governing cell plasticity and cell quiescence using zebrafish and human cells. The decision for cells to proliferate or not plays key roles in development, tissue repair, and regeneration. Compared with our extensive understanding of the cell cycle, however, we have limited knowledge of how the cellular quiescence state is regulated. Our current studies focus on discovering cell-autonomous and non-autonomous mechanisms regulating the entry, maintenance, and exit of the cellular quiescent state. We have developed a zebrafish model, in which a population of quiescent cells can be induced to reenter the cell cycle and proliferate. Using this whole animal platform, in vivo imaging, CRISPR/Cas9 gene editing, chemical biology, and RNAseq analyses have led to the discovery of a number of key regulators governing the cell quiescence-proliferation decision. Many of them are converged onto the insulin/insulin-like growth factor (IIS)-PI3 kinase-Akt-mTor signaling pathway.