Since the establishment of mouse embryonic stem cells (mESCs) in the 1980s, a number of important notions on the self-renewal of pluripotent stem cells in vitro have been found. In serum containing conventional culture, an exogenous cytokine, leukemia inhibitory factor (LIF), is absolutely essential for the maintenance of pluripotency. In contrast, in serum-free culture with simultaneous inhibition of Map-kinase and Gsk3 (so called 2i-culture), LIF is no longer required. However, recent findings also suggest that LIF may have a role not covered by the 2i for the maintenance of naïve pluripotency. These suggest that LIF functions for the maintenance of naïve pluripotency in a context dependent manner. We summarize how LIF-signal pathway is converged to maintain the naïve state of pluripotency.
Keywords: Embryonic stem cell (ESC), Lekemia inhibitory factor (LIF) signal, Stat3, MAP kinase, PI3K-Akt, Genetic background, naive state of pluripoetncy, Epigenetics.