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08:21
In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells
Published on: March 16, 2017
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Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification
Rosalia Fernandez-Alonso1, Lindsay Davidson2, Jens Hukelmann3
1The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, The University of Dundee, Dundee, UK.
EMBO Reports
|June 8, 2017
Summary
BET proteins regulate stem cell differentiation. Brd4 maintains pluripotency, while Brd2 promotes lineage specification by activating Nodal signaling, coordinating stem cell fate decisions.
Area of Science:
- Stem cell biology
- Molecular mechanisms of cell differentiation
- Epigenetics and gene regulation
Background:
- Pluripotent stem cells (PSCs) can differentiate into specialized tissues, but the mechanisms controlling this process are unclear.
- The Smad2 signaling network is crucial for determining PSC fate.
Purpose of the Study:
- To identify novel regulators of Smad2 signaling in PSCs.
- To elucidate the role of BET proteins in coordinating pluripotent exit and lineage specification.
Main Methods:
- Small molecule screening to identify Smad2 signaling regulators.
- Analysis of BET protein function and localization at Nodal gene regulatory elements (NREs).
Main Results:
- BET family bromodomain proteins are essential for Smad2 activation.
- BET proteins engage NREs to promote Nodal signaling and Smad2 responses.
- Brd4 maintains pluripotency, while Brd2 promotes differentiation by binding NREs after Brd4 downregulation.
Conclusions:
- Distinct BET protein functions and isoform switching (Brd4-Brd2) at NREs coordinate pluripotent exit with lineage specification.
- Brd2 plays a specific role in differentiative Nodal-Smad2 signaling.
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