Systematic reconstruction of cellular trajectories across mouse embryogenesis

Area of Science:

• Developmental Biology
• Genomics
• Computational Biology

Background:

• Mammalian embryogenesis involves rapid cell proliferation and diversification from a single zygote.
• Understanding the major cellular trajectories during in vivo mammalian development is challenging.
• Existing studies lack a comprehensive map of developmental pathways.

Purpose of the Study:

• To integrate multiple single-cell RNA-sequencing datasets to create a comprehensive map of mammalian embryogenesis.
• To define cell states and their trajectories from early embryonic stages through organogenesis.
• To identify candidate regulatory transcription factors and conserved cell types across vertebrates.

Main Methods:

• Integration of existing and newly generated single-cell RNA-sequencing data from mouse embryos.
• Profiling of approximately 150,000 nuclei from embryonic day 8.5 (E8.5) embryos.
• Construction of a directed acyclic graph (TOME) to represent developmental trajectories.

Main Results:

• Defined 19 successive cell states spanning embryonic development from E3.5 to E13.5.
• Created a computational model (TOME) illustrating cell state transitions and relationships.
• Identified candidate transcription factors regulating cell-type specification and homologous cell types across vertebrates.

Conclusions:

• The TOME model provides a detailed map of mammalian embryogenesis, largely consistent with current knowledge.
• This resource facilitates the systematic identification of developmental regulators.
• The study offers insights into conserved cell-type evolution in vertebrates.