An integrated approach identifies the molecular underpinnings of murine anterior visceral endoderm migration.

The anterior visceral endoderm (AVE) differs from the surrounding visceral endoderm (VE) in its migratory behavior and ability to restrict primitive streak formation to the opposite side of the mouse embryo. To characterize the molecular bases for the unique properties of the AVE, we combined single-cell RNA sequencing of the VE prior to and during AVE migration with phosphoproteomics, high-resolution live-imaging, and short-term lineage labeling and intervention. This identified the transient nature of the AVE with attenuation of "anteriorizing" gene expression as cells migrate and the emergence of heterogeneities in transcriptional states relative to the AVE's position. Using cell communication analysis, we identified the requirement of semaphorin signaling for normal AVE migration. Lattice light-sheet microscopy showed that Sema6D mutants have abnormalities in basal projections and migration speed. These findings point to a tight coupling between transcriptional state and position of the AVE and identify molecular controllers of AVE migration.

A comprehensive review: synergizing stem cell and embryonic development knowledge in mouse and human integrated stem cell-based embryo models.

Mammalian stem cell-based embryo models have emerged as innovative tools for investigating early embryogenesis in both mice and primates. They not only reduce the need for sacrificing mice but also overcome ethical limitations associated with human embryo research. Furthermore, they provide a platform to address scientific questions that are otherwise challenging to explore in vivo. The usefulness of a stem cell-based embryo model depends on its fidelity in replicating development, efficiency and reproducibility; all essential for addressing biological queries in a quantitative manner, enabling statistical analysis. Achieving such fidelity and efficiency requires robust systems that demand extensive optimization efforts. A profound understanding of pre- and post-implantation development, cellular plasticity, lineage specification, and existing models is imperative for making informed decisions in constructing these models. This review aims to highlight essential differences in embryo development and stem cell biology between mice and humans, assess how these variances influence the formation of partially and fully integrated stem cell models, and identify critical challenges in the field.