Stem Cell Institute, Division of Haematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Biochem J. 2011 Aug 15;438(1):11-23. doi: 10.1042/BJ20102152.
LIF (leukaemia inhibitory factor) is a key cytokine for maintaining self-renewal and pluripotency of mESCs (mouse embryonic stem cells). 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 mESCs. 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. The fundamental role of LIF for pluripotency was highlighted further by the discovery that LIF accelerates the conversion of epiblast-derived stem cells into a more fully pluripotent state. In the present review, we provide an overview of the three major LIF signalling pathways, the molecules that interact with STAT3 and the current interpretations of the roles of LIF in pluripotency.
LIF（白血病抑制因子）是维持 mESCs（小鼠胚胎干细胞）自我更新和多能性的关键细胞因子。LIF 与 LIF 受体结合后，激活三条主要的细胞内信号通路：JAK（Janus 激酶）/STAT3（信号转导和转录激活因子 3）、PI3K（磷酸肌醇 3-激酶）/AKT 和 SHP2 [SH2（Src 同源 2 结构域）域含有酪氨酸磷酸酶 2]/MAPK（丝裂原激活的蛋白激酶）途径。这些途径协同作用，协调 mESCs 特有的基因表达模式。在 LIF 受体的许多信号事件中，转录因子 STAT3 的激活和 DNA 结合在转导 LIF 的功能中起着核心作用。LIF 对多能性的基本作用进一步突出表现在发现 LIF 加速了上胚层衍生的干细胞向更完全的多能状态的转化。在本综述中，我们概述了 LIF 的三条主要信号通路、与 STAT3 相互作用的分子以及 LIF 在多能性中的作用的当前解释。
