NKX2-1 Activation by SMAD2 Signaling After Definitive Endoderm Differentiation in Human Embryonic Stem Cell
Copyright policy )NKX2-1 Activation by SMAD2 Signaling After Definitive Endoderm Differentiation in Human Embryonic Stem Cell
Expression of NKX2-1 is required to specify definitive endoderm to respiratory endoderm. However, the transcriptional regulation of NKX2-1 is not fully understood. Here we demonstrate that aside from specifying undifferentiated human embryonic stem cell (hESC) to definitive endoderm, high concentrations of Activin-A are also necessary and sufficient to induce hESC-derived definitive endodermal progeny to a FOXA2/NKX2-1/GATA6/PAX9 positive respiratory epithelial fate. Activin-A directly mediates the induction of NKX2-1 by interacting with ALK4, leading to phosphorylation of SMAD2, which binds directly to the NKX2-1 promoter and activates its expression. Activin-A can be replaced by GDF11 but not transforming growth factor β1. Addition of Wnt3a, SHH, FGF2, or BMP4 failed to induce NKX2-1. These results suggest that direct binding of Activin-A-responsive SMAD2 to the NKX2-1 promoter plays essential role during respiratory endoderm specification.
- Katholieke Universiteit Leuven Belgium
- KU Leuven Belgium
Binding Sites, Endoderm, Respiratory System, Thyroid Nuclear Factor 1, Nuclear Proteins, Cell Differentiation, Smad2 Protein, Activins, Cell Line, Growth Differentiation Factors, Gene Expression Regulation, Bone Morphogenetic Proteins, Humans, Phosphorylation, Promoter Regions, Genetic, Protein Processing, Post-Translational, Embryonic Stem Cells, Protein Binding, Signal Transduction, Transcription Factors
Binding Sites, Endoderm, Respiratory System, Thyroid Nuclear Factor 1, Nuclear Proteins, Cell Differentiation, Smad2 Protein, Activins, Cell Line, Growth Differentiation Factors, Gene Expression Regulation, Bone Morphogenetic Proteins, Humans, Phosphorylation, Promoter Regions, Genetic, Protein Processing, Post-Translational, Embryonic Stem Cells, Protein Binding, Signal Transduction, Transcription Factors
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).14 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!