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

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 endod...

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Bibliographic Details
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
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Online Access:https://hdl.handle.net/10356/171666
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Institution: Nanyang Technological University
Language: English
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Summary: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.