The primitive endoderm supports lineage plasticity to enable regulative development.

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Epigenetics

Background:

• Mammalian blastocyst formation requires trophectoderm specification and inner cell mass differentiation into epiblast and primitive endoderm (PrE).
• Embryos possess a window of developmental plasticity, allowing cellular fate redirection.
• The role of the PrE in blastocyst regeneration and plasticity remains incompletely understood.

Purpose of the Study:

• To investigate the regenerative capacity of the primitive endoderm (PrE) in mammalian blastocyst formation.
• To identify and characterize in vitro stem cell populations with blastocyst-forming potential.
• To elucidate the molecular mechanisms suppressing PrE commitment and maintaining developmental plasticity.

Main Methods:

• Experimental manipulation of early mammalian embryos.
• In vitro culture of stem cell populations.
• Analysis of gene expression, transcription factor activity, and enhancer landscapes.
• JAK/STAT signaling pathway inhibition and OCT4 expression studies.

Main Results:

• The primitive endoderm (PrE) alone is sufficient to regenerate a complete blastocyst and support post-implantation development.
• An in vitro PrE-like population was identified with embryonic and extra-embryonic potency, capable of forming stem cell-based embryo models (blastoids).
• JAK/STAT signaling, OCT4, and sustained pluripotency transcription factors suppress PrE commitment by maintaining a permissive enhancer landscape.

Conclusions:

• The primitive endoderm (PrE) possesses significant regenerative potential, capable of forming complete blastocysts.
• Sustained transcription factor activity is crucial for maintaining developmental plasticity in regulative development.
• The PrE plays a critical role in embryonic development, particularly under perturbed conditions, and is key to blastoid formation.