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Role of CEBPa in trophectoderm competence installment
Xiao Wei1, Irepan Salvador-Martinez2, Maciej Meglicki3
1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.
Science Advances
|November 28, 2025
Summary
The transcription factor CEBPa (CCAAT enhancer-binding protein alpha) is crucial for trophectoderm (placenta) development in mouse embryos. Its early upregulation establishes trophectoderm competence before lineage specification.
Area of Science:
- Developmental Biology
- Genetics
- Epigenetics
Background:
- Mouse embryogenesis involves progressive loss of totipotency.
- Blastomeres differentiate into trophectoderm and inner cell mass starting at the 16-cell stage.
- The timing and mechanisms of lineage specification competence acquisition remain unclear.
Purpose of the Study:
- To investigate the role of CEBPa in early mouse embryonic lineage specification.
- To determine when and how blastomeres gain competence for trophectoderm differentiation.
- To identify CEBPa-regulated targets involved in trophectoderm development.
Main Methods:
- Analysis of CEBPa expression dynamics during mouse embryogenesis.
- CRISPR-Cas9 gene knockout of CEBPa in mouse embryos.
- Overexpression of CEBPa in mouse embryonic stem cells.
- Identification and characterization of CEBPa-bound enhancers using functional assays.
Main Results:
- CEBPa is upregulated from the two- to four-cell stage, regulated by NR5A2.
- CEBPa knockout embryos show reduced trophectoderm proportion and delayed blastocyst formation.
- CEBPa overexpression in stem cells induces trophectoderm-like differentiation.
- CEBPa regulates specific enhancers active in early trophectoderm development.
Conclusions:
- CEBPa plays a critical role in establishing trophectoderm competence prior to the first lineage bifurcation.
- CEBPa is essential for subsequent trophectoderm specification and development.
- CEBPa-regulated enhancers are activated early, priming trophectoderm development.
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