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Updated: Jul 24, 2025
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In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells
Published on: March 16, 2017
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EP300 facilitates human trophoblast stem cell differentiation.
A Jantine van Voorden1, Remco Keijser1, Geertruda J M Veenboer1
1Reproductive Biology Laboratory, Amsterdam Reproduction & Development, Amsterdam University Medical Centers, University of Amsterdam 1105 AZ, Amsterdam, the Netherlands.
Summary
EP300, not CREBBP, is crucial for early human placenta development. EP300 regulates trophoblast differentiation by impacting EGFR signaling, and its deficiency is linked to pregnancy complications.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Early placenta development requires cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB).
- Defective trophoblast development is linked to pregnancy complications like fetal growth restriction and pre-eclampsia.
- Rubinstein-Taybi syndrome, caused by mutations in CREBBP or EP300, is associated with increased pregnancy complications, particularly with EP300 mutations.
Purpose of the Study:
- To investigate the role of EP300 and CREBBP in early human trophoblast differentiation.
- To understand the molecular mechanisms underlying EP300's role in placentation.
- To correlate EP300's function with pregnancy complications observed in Rubinstein-Taybi syndrome.
Main Methods:
- Utilized human trophoblast stem cells (TSCs) and trophoblast organoids.
- Employed pharmacological inhibition of CREBBP/EP300.
- Used RNA interference and CRISPR/Cas9 for gene knockdown.
- Performed transcriptome sequencing to identify gene expression changes.
- Investigated the effect of TGF-α supplementation.
Main Results:
- Pharmacological inhibition of CREBBP/EP300 blocked trophoblast differentiation and expanded TSC-like cells.
- Knockdown of EP300, but not CREBBP, inhibited trophoblast differentiation.
- EP300 knockdown led to upregulation of transforming growth factor alpha (TGFA).
- TGF-α supplementation mimicked EP300 knockdown effects on differentiation and proliferation.
- EP300 appears to regulate trophoblast differentiation via EGFR signaling.
Conclusions:
- EP300 plays a critical role in human trophoblast differentiation and early placentation.
- EP300 facilitates differentiation by modulating EGFR signaling pathways.
- EP300 deficiency contributes to pregnancy complications associated with Rubinstein-Taybi syndrome.
