Single-cell patterning and axis characterization in the murine and human definitive endoderm.

Area of Science:

• Developmental Biology
• Genomics
• Organogenesis

Background:

• Precise regionalization of definitive endoderm progenitors is crucial for understanding respiratory and digestive organ development.
• Endoderm progenitor patterning is not fully resolved, especially in humans.

Purpose of the Study:

• To define endoderm regions and developmental pathways using single-cell RNA sequencing.
• To identify cell subpopulations, spatial distributions, and molecular features.
• To compare endoderm patterning between mice and humans.

Main Methods:

• Single-cell RNA sequencing of endoderm cells during early somitogenesis.
• Development of molecular criteria to define four major endoderm regions.
• Analysis of cell subpopulations, spatial distribution, and molecular features.

Main Results:

• Defined four major endoderm regions (foregut, lip of anterior intestinal portal, midgut, hindgut) and their developmental pathways.
• Identified cell subpopulations and their spatial distributions within each region.
• Dorsal and ventral pancreatic progenitors originate from the midgut but follow distinct developmental pathways.

Conclusions:

• Comprehensive definition of single-cell endoderm patterning.
• Novel insights into the spatiotemporal processes establishing early endoderm domains.
• Identified conserved endoderm patterning in humans with notable differences in dorsal cell distribution compared to mice.