FGF signaling mediates definitive endoderm formation by regulating epithelial-to-mesenchymal transition and cell proliferation

• Published in: The International journal of developmental biology Vol. 64; no. 10-11-12; pp. 471 - 477
• Main Authors: Li, Shengbiao, Huang, Qingsong, Mao, Jianwen, Li, Qiuhong
• Format: Journal Article
• Language: English
• Published: Spain University of the Basque Country Press 2020
• Subjects: Cell adhesion; Cell adhesion & migration; Cell differentiation; Cell growth; Cell proliferation; Differentiation; E-cadherin; Embryo cells; Endoderm; Fibroblast growth factors; Kinases; Mesenchyme; Signal transduction; Signaling; Snail protein; Stem cells; Transcription activation; Zinc finger proteins
• ISSN: 0214-6282; 1696-3547
• DOI: 10.1387/ijdb.190372ql

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.