FGF signaling mediates definitive endoderm formation by regulating epithelial-to-mesenchymal transition and cell proliferation
FGF signaling mediates definitive endoderm formation by regulating epithelial-to-mesenchymal transition and cell proliferation
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FGF信号通过调节上皮间质转化和细胞增殖介导定形内胚层形成
DOI：
10.1387/ijdb.190372ql
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发表时间：
2020-01-01
影响因子：
0.7
通讯作者：
Li, Qiuhong
中科院分区：
文献类型：
--
作者：
Li, Shengbiao;Huang, Qingsong;Li, Qiuhong
人胚胎干细胞（human embryonic stem cells，hESCs）向定形内胚层（definitive endoderm，DE）分化需要FGF信号通路的参与，而DE的分化往往伴随着上皮细胞向间充质细胞转化（epithelial-to-mesenchymal transition，EMT）的过程。然而，在体外DE形成过程中FGF信号传导和EMT之间是否存在关联仍然是难以捉摸的。在本研究中，我们确定了几个FGF家族成员显着激活过程中向DE分化的hESCs。通过有效的和选择性的抑制剂BGJ 398抑制FGF信号传导，通过阻断锌指转录因子SNAI 1（其是细胞粘附蛋白CDH 1的直接转录阻遏物）的激活来消除EMT和DE诱导。此外，减弱FGF信号传导也严重影响细胞增殖。综上所述，我们认为FGF信号通过介导EMT和细胞增殖促进DE的形成。
FGF signaling pathway is imperative for definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs), which always accompanies an epithelial-to-mesenchymal transition (EMT) process. However, whether there is an association between FGF signaling and the EMT during DE formation in vitro has remained elusive. In the present study, we identify that several FGF family members were significantly activated during the differentiation of hESCs toward DE. Inhibition of FGF signaling by an efficient and selective inhibitor BGJ398 abolishes both the EMT and DE induction by blocking the activation of the zinc-finger transcription factor SNAI1 which is a direct transcriptional repressor of cell adhesion protein CDH1. In addition, cell proliferation is also severely influenced by attenuating the FGF signaling. Collectively, we propose that the FGF signaling promotes the DE formation through mediating the EMT and cell proliferation.