Single-Cell RNA Sequencing of Sox17-Expressing Lineages Reveals Distinct Gene Regulatory Networks and Dynamic...

Area of Science:

• Developmental Biology
• Genetics
• Cell Biology

Background:

• SOX17 (SRY-box transcription factor 17) is essential for early embryogenesis.
• It plays a role in forming the hepato-pancreato-biliary system and vascular-hematopoietic emergence.

Purpose of the Study:

• To investigate the function of SOX17 in the developing endoderm and endothelium.
• To analyze cell-type-specific gene regulatory networks controlled by SOX17.

Main Methods:

• Developed a dual-color temporal lineage-tracing strategy in mice.
• Performed single-cell RNA sequencing on 6934 cells from SOX17-expressing lineages at embryonic days 9.0-9.5.
• Utilized differential gene expression, trajectory, and RNA-velocity analyses.

Main Results:

• Identified 19 distinct cellular clusters across three germ layers.
• Revealed heterogeneous endothelial cell populations, including two hemogenic subsets from different origins.
• Discovered subsets of hepatic, pancreatic, and biliary progenitors with overlapping developmental potential in the posterior foregut endoderm.
• Calculated gene-regulatory networks showing lineage-specific transcription factor dominance.

Conclusions:

• SOX17 exhibits distinct regulons in endoderm versus endothelial cells.
• SOX17 interacts differentially with other factors to mediate lineage-specific regulatory actions.
• This highlights SOX17's critical, context-dependent role in cell fate determination during embryogenesis.