Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during...

Area of Science:

• Developmental biology
• Stem cell biology
• Genomics

Background:

• Visceral organs develop from the fetal foregut via interactions between definitive endoderm (DE) and splanchnic mesoderm (SM).
• Mechanisms of SM regionalization and coordination with epithelial identity remain poorly understood, unlike DE patterning.

Purpose of the Study:

• To create a high-resolution cell state map of the embryonic mouse foregut.
• To identify and characterize the spatiotemporal signaling network orchestrating foregut organogenesis.
• To generate elusive SM subtypes from human pluripotent stem cells (hPSCs).

Main Methods:

• Single-cell transcriptomics of embryonic mouse foregut.
• Inference of endoderm-mesoderm signaling networks.
• Mouse genetics for validation.
• Directed differentiation of hPSCs.

Main Results:

• Identified diverse SM cell types developing in register with organ-specific epithelia.
• Inferred a signaling network critical for foregut organogenesis.
• Validated the importance of endoderm-derived signals in SM patterning using mouse models.
• Successfully generated distinct SM subtypes from hPSCs.

Conclusions:

• Endoderm-derived signals play a critical role in patterning the splanchnic mesoderm during foregut development.
• The study provides a valuable resource for understanding organogenesis and developing regenerative therapies.
• This work advances the ability to generate specific mesodermal cell types from pluripotent stem cells.