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A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
Activin/Nodal signalling maintains pluripotency by controlling Nanog expression
Ludovic Vallier1, Sasha Mendjan, Stephanie Brown
1Department of Surgery and Laboratory For Regenerative Medicine, West Forvie Building, Robinson Way, University of Cambridge, Cambridge CB2 0SZ, UK. lv225@cam.ac.uk
Development (Cambridge, England)
|March 13, 2009
Summary
Activin/Nodal signaling maintains pluripotency in human ESCs by controlling Nanog expression. Nanog then blocks differentiation into neuroectoderm and endoderm, preserving stem cell potential.
Area of Science:
- Stem cell biology
- Developmental biology
- Signaling pathways
Background:
- Embryonic stem cells (ESCs) possess pluripotency, enabling differentiation into all adult cell types.
- Understanding pluripotency mechanisms is crucial for therapeutic applications of differentiated cells.
- Activin/Nodal signaling is vital for maintaining pluripotency in human ESCs and mouse EpiSCs, but its precise role is unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms by which Activin/Nodal signaling maintains pluripotency in human ESCs and mouse EpiSCs.
- To investigate the role of Nanog in mediating the effects of Activin/Nodal signaling on pluripotency.
Main Methods:
- Investigated the regulation of Nanog expression by Activin/Nodal signaling in human ESCs and mouse EpiSCs.
- Assessed the impact of Nanog on differentiation pathways induced by FGF signaling and Smad2/3 activity.
Main Results:
- Activin/Nodal signaling directly controls the expression of the pluripotency factor Nanog in both human ESCs and mouse EpiSCs.
- Nanog acts to inhibit neuroectoderm differentiation triggered by FGF signaling.
- Nanog also restricts the transcriptional activity of the Smad2/3 cascade, preventing endoderm lineage progression.
Conclusions:
- A negative-feedback loop involving Activin/Nodal, Nanog, and differentiation pathways maintains stem cell pluripotency.
- This loop imposes a state of stasis, preventing premature differentiation and preserving the pluripotent status of human ESCs and mouse EpiSCs.
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