Decoding anterior-posterior axis emergence among mouse, monkey, and human embryos

Anterior-posterior axis formation regulated by the distal visceral endoderm (DVE) and anterior visceral endo-derm (AVE) is essential for peri-implantation embryogenesis. However, the principles of the origin and specialization of DVE and AVE remain elusive. Here, with single-cell transcriptome analysis and pseudotime prediction, we show that DVE and AVE independently originate from the specialized primary endoderm in mouse blastocysts. Along distinct developmental paths, these two lineages, respectively, undergo four representative states with stage-specific transcriptional patterns around implantation. Further comparative analysis shows that AVE, but not DVE, is detected in human and non-human primate embryos, defining differences in polarity formation across species. Moreover, stem cell-assembled human blastoids lack DVE or AVE precursors, implying that additional induction of stem cells with DVE/AVE potential could promote the current embryo-like models and their post-implantation growth. Our work provides insight into understanding of embryonic polarity formation and early mammalian development.

Automated summary

We used single-cell transcriptome analysis to study the origin and specialization of distal visceral endoderm (DVE) and anterior visceral endoderm (AVE) in mouse blastocysts. We found that DVE and AVE independently originate from specialized primary endoderm and that AVE is also present in human and non-human primate embryos, indicating differences in polarity formation across species. Stem cell-assembled human blastoids lack DVE or AVE precursors, suggesting the potential to improve current embryo-like models by inducing stem cells with DVE/AVE potential.