Abstract
Pluripotent stem cells (PSCs) isolated in vitro 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.
Highlights
Pluripotent stem cells (PSCs) display two remarkable characteristics
We summarize the role of fibroblast growth factor (FGF) signaling in the maintenance of pluripotency state of stem cells through regulation of key transcriptional factors
Fibroblast growth factor 5 is well known as a mouse EpiESCs (mEpiSCs) or epiblast marker, its expression is generally associated with differentiation and loss of stemness, FGF5 is hardly detectable in mouse embryonic stem cell (mESC). mEpiSCs as primed state PSCs, are characterized by expressing markers such as Fgf5, T-Brachyury, Cer1, Otx2, Socs3, Acvr2b, and Lefty whereas mESC expressed Rex1, krueppellike factor 4 (Klf4), and Nanog (Nichols and Smith, 2011)
Summary
Pluripotent stem cells (PSCs) display two remarkable characteristics. Firstly, they are capable of giving rise to every somatic cell originating from all three germ layers (endoderm, mesoderm, and ectoderm) but not the extraembryonic tissues. We summarize the role of FGF signaling in the maintenance of pluripotency state of stem cells through regulation of key transcriptional factors.
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