FGFR-mediated ERK1/2 signaling contributes to mesendoderm and definitive endoderm formation in vitro

• Main Authors: Lau, Hwee Hui, Amirruddin, Nur Shabrina, Loo, Larry Sai Weng, Chan, Jun Wei, Iich, Elhadi, Krishnan, Vidhya Gomathi, Hoon, Shawn, Teo, Adrian Kee Keong
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; Developmental Biology; Embryology
• Online Access: https://hdl.handle.net/10356/171666
• Institution: Nanyang Technological University

The differentiation of human pluripotent stem cells into the SOX17+ definitive endoderm (DE) germ layer is important for generating tissues for regenerative medicine. Multiple developmental and stem cell studies have demonstrated that Activin/Nodal signaling is the primary driver of definitive endoderm formation. Here, we uncover that the FGF2-FGFR-ERK1/2 signaling contributes to mesendoderm and SOX17+ DE formation. Without ERK1/2 signaling, the Activin/Nodal signaling is insufficient to drive mesendoderm and DE formation. Besides FGF2-FGFR-mediated signaling, IGF1R signaling possibly contributes to the ERK1/2 signaling for DE formation. We identified a temporal relationship between Activin/Nodal-SMAD2 and FGF2-FGFR-ERK1/2 signaling in which Activin/Nodal-SMAD2 participates in the initiation of mesendoderm and DE specification that is followed by increasing activity of FGF2-FGFR-ERK1/2 to facilitate and permit the successful generation of SOX17+ DE. Overall, besides the role of Activin/Nodal signaling for DE formation, our findings shed light on the contribution of ERK1/2 signaling for mesendoderm and DE formation.