Generative model for the first cell fate bifurcation in mammalian development

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• The first cell fate decision in mammalian embryos separates cells into trophectoderm (TE) and inner cell mass (ICM) lineages.
• This bifurcation is regulated by the YAP transcriptional co-activator's subcellular localization.
• Reconstructing TE/ICM specification dynamics is challenging due to asynchronous cell divisions and blastomere arrangement.

Purpose of the Study:

• To develop a live imaging approach to dynamically track key factors in early cell fate decisions.
• To construct a generative model of the first cell fate bifurcation in mammalian development.
• To understand the stochastic nature and temporal dynamics of TE/ICM cell specification.

Main Methods:

• Developed a live imaging technique for preimplantation embryos.
• Measured nuclear YAP dynamics and its target genes (CDX2 for TE, SOX2 for ICM).
• Constructed a generative model based on live imaging data to analyze cell fate allocation statistics.

Main Results:

• The generative model accurately depicts time-dependent TE/ICM cell allocation.
• Revealed stochastic timing in the induction of key cell fate determinants (YAP, CDX2, SOX2).
• Identified specific YAP dynamics essential for inducing cell fate; noted prominent temporal heterogeneity in SOX2 expression within ICM cells.

Conclusions:

• The study elucidates the dynamic mechanisms governing the first mammalian cell fate bifurcation.
• Highlights the stochasticity and temporal heterogeneity in early cell fate determination, particularly in ICM development.
• Provides a foundation for investigating subsequent cell fate decisions in mammalian embryogenesis.