2. Academic Validation
  3. Role of CEBPa in trophectoderm competence installment

Role of CEBPa in trophectoderm competence installment

  • Sci Adv. 2025 Nov 28;11(48):eady1693. doi: 10.1126/sciadv.ady1693.
Xiao Wei 1,  Irepan Salvador-Martinez 2,  Maciej Meglicki 3,  Marcos Plana-Carmona 1,  Antonios Klonizakis 1,  Barbara Pernaute 1,  Manuel Irimia 1 4 5,  Gregoire Stik 1,  Mina Popovic 6,  Guillem Torcal Garcia 1,  Holger Heyn 2 5 7,  Magdalena Zernicka-Goetz 3 8,  Thomas Graf 1 4
Affiliations

Affiliations

  • 1 Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.
  • 2 Single Cell Genomics, Centro Nacional de Análisis Genómico, Barcelona 08028, Spain.
  • 3 Mammalian Embryo and Stem Cell Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
  • 4 Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona 08005, Spain.
  • 5 ICREA, Pg. Lluis Companys 23, Barcelona 08010, Spain.
  • 6 Research and Development, Eugin Group, Barcelona 08006, Spain.
  • 7 Universitat de Barcelona (UB), Barcelona 08007, Spain.
  • 8 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
PMID: 41313781 DOI: 10.1126/sciadv.ady1693
Abstract

During mouse embryogenesis, totipotency is gradually lost, and, at the 16-cell stage, blastomeres begin to bifurcate into trophectoderm (future placenta) and inner cell mass (future fetus). Although this process is well studied, when and how blastomeres acquire the competence for lineage specification remains unclear. Here, we describe that CEBPa becomes up-regulated at the transition from the two- to the four-cell stage by NR5A2 and is also selectively expressed in the trophectoderm at the blastocyst stage. Its knockout decreases the proportion of trophectoderm cells and delays the morula to blastocyst transition. Conversely, CEBPa overexpression in mouse embryonic stem cells, used as a proxy, drives their differentiation into trophectoderm-like cells, enabling the identification of CEBPa-regulated trophectoderm-specific enhancers. A subset of these enhancers, associated with key trophectoderm-related transcription factor genes, is primed or activated in four- and eight-cell embryos. Together, our data suggest that CEBPa plays a role in the installment of trophectoderm competence before the first lineage bifurcation and in trophectoderm specification.

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