LIF (leukaemia inhibitory factor) is commonly used to maintain mouse embryonic stem cells in an undifferentiated state. Leukemia inhibitory factor (LIF) is capable of maintaining embryonic stem (ES) cells in a pluripotent state through promoting self-renewal or suppressing stem cell differentiation. It has become a standard protocol to use LIF to maintain murine embryonic stem cell pluripotency, whereas withdrawal of LIF allows embryonic stem cells to undergo cell differentiation. Upon withdrawal of both LIF and feeder cells, embryonic stem cells are able to，differentiate spontaneously into various cell types in three primitive layers.
Upon binding to the LIF receptor, LIF activates three major intracellular signalling pathways: the JAK (Janus kinase)/STAT3 (signal transducer and activator of transcription 3), PI3K (phosphoinositide 3-kinase)/AKT and SHP2 [SH2 (Src homology 2) domain-containing tyrosine phosphatase 2]/MAPK (mitogen-activated protein kinase) pathways. These pathways converge to orchestrate the gene expression pattern specific to mouse embryonic stem cells. Among the many signalling events downstream of the LIF receptor, activation and DNA binding of the transcription factor STAT3 plays a central role in transducing LIF's functions.
As a pleiotropic factor, LIF has been proven to have a wide array of actions during the process of neural stem cell differentiation into neuronal and glial cells. In the central nervous system, the LIF signaling pathway synergistically with other signaling pathways to inhibit the differentiation of neural stem cells along a glial lineage. However, LIF downstream factor STAT3, in combination with other factors, selectively promotes fetal neural stem cell differentiation toward a glial fate. During neuraln crest cell differentiation, LIF enhances the survival of sensory neurons and stimulates their formation from neuralcrest progenitor cells.
• He Z, et al. Effect of leukemia inhibitory factor on embryonic stem cell differentiation: implications for supporting neuronal differentiation[J]. Acta Pharmacologica Sinica, 2006, 27(1): 80-90.
• Hirai H, et al. Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor[J]. Biochemical Journal, 2011, 438(1): 11-23.