Mossahebi-Mohammadi Majid, Quan Meiyu, Zhang Jin-San, Li Xiaokun
School of Pharmaceutical Sciences and International Collaborative Center on Growth Factor Research, Wenzhou Medical University, Wenzhou, China.
Institute of Life Sciences, Wenzhou University, Wenzhou, China.
Front Cell Dev Biol. 2020 Feb 18;8:79. doi: 10.3389/fcell.2020.00079. eCollection 2020.
Pluripotent stem cells (PSCs) isolated from embryonic stem cells (ESCs), induced PSC (iPSC) and also post-implantation epiblast-derived stem cells (EpiSCs) are known for their two unique characteristics: the ability to give rise to all somatic lineages and the self-renewal capacity. Numerous intrinsic signaling pathways contribute to the maintenance of the pluripotency state of stem cells by tightly controlling key transcriptional regulators of stemness including sex determining region Y box 2 (Sox-2), octamer-binding transcription factor (Oct)3/4, krueppel-like factor 4 (Klf-4), Nanog, and c-Myc. Signaling by fibroblast growth factor (FGF) is of critical importance in regulating stem cells pluripotency. The FGF family is comprised of 22 ligands that interact with four FGF receptors (FGFRs). FGF/FGFR signaling governs fundamental cellular processes such as cell survival, proliferation, migration, differentiation, embryonic development, organogenesis, tissue repair/regeneration, and metabolism. FGF signaling is mediated by the activation of RAS - mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT, Phospholipase C Gamma (PLCγ), and signal transducers and activators of transcription (STAT), which intersects and synergizes with other signaling pathways such as Wnt, retinoic acid (RA) and transforming growth factor (TGF)-β signaling. In the current review, we summarize the role of FGF signaling in the maintenance of pluripotency state of stem cells through regulation of key transcriptional factors.
从胚胎干细胞（ESC）、诱导多能干细胞（iPSC）以及植入后上胚层来源的干细胞（EpiSC）中分离出的多能干细胞（PSC）具有两个独特的特征：能够分化为所有体细胞谱系以及自我更新能力。众多内在信号通路通过严格控制干性的关键转录调节因子，包括性别决定区Y框2（Sox-2）、八聚体结合转录因子（Oct）3/4、克鲁ppel样因子4（Klf-4）、Nanog和c-Myc，来维持干细胞的多能性状态。成纤维细胞生长因子（FGF）信号在调节干细胞多能性方面至关重要。FGF家族由22种配体组成，它们与四种FGF受体（FGFR）相互作用。FGF/FGFR信号控制着细胞存活、增殖、迁移、分化、胚胎发育、器官形成、组织修复/再生和代谢等基本细胞过程。FGF信号由RAS-丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K）-AKT、磷脂酶Cγ（PLCγ）以及信号转导和转录激活因子（STAT）的激活介导，这些信号与Wnt、视黄酸（RA）和转化生长因子（TGF）-β信号等其他信号通路相互交叉并协同作用。在本综述中，我们总结了FGF信号通过调节关键转录因子在维持干细胞多能性状态中的作用。
