Cross-species single-cell transcriptomic analysis reveals pre-gastrulation developmental differences among pigs,...

Area of Science:

• Developmental Biology
• Comparative Genomics
• Stem Cell Biology

Background:

• Interspecies blastocyst complementation offers a potential route for generating human organs in animal hosts.
• Significant barriers exist in efficient xenogeneic chimera formation due to interspecies developmental incompatibilities.

Purpose of the Study:

• To construct a comprehensive single-cell landscape of early pig embryonic development.
• To systematically compare pig epiblast development with human and monkey development.
• To identify species-specific differences that impede human-pig chimerism.

Main Methods:

• Single-cell RNA sequencing to create a developmental atlas of early pig embryos.
• Comparative analysis of epiblast development across pigs, humans, and monkeys.
• Identification of molecular and cellular differences in pluripotency, metabolism, epigenetics, cell surface proteins, and trophectoderm development.

Main Results:

• A conserved pluripotency spectrum was identified across pigs, humans, and monkeys.
• Significant species-specific divergences were revealed in pluripotency progression, metabolic shifts, epigenetic/transcriptional regulation, cell surface markers, and trophectoderm development.
• These differences likely impair human cell recognition, communication, integration, and survival within pig embryos.

Conclusions:

• Understanding species-specific developmental differences is crucial for overcoming low human-pig chimerism.
• The identified divergences provide insights into conserved and divergent mammalian developmental processes.
• These findings are essential for developing strategies to enable functional human organ generation in pigs.