Application of single-cell transcriptomic technology in cell fate determination of embryonic liver.

Single-cell transcriptomics has revolutionized our understanding of embryonic liver development by enabling high-resolution dissection of lineage specification and cellular interactions. In this review, we synthesize recent advances from scRNA sequencing, spatial transcriptomics, multi-omics integration, and organoid modeling, with attention to both human and mouse embryonic contexts. These studies have delineated the bifurcation of hepatoblasts into hepatocytes and cholangiocytes, uncovered Hepatobiliary hybrid progenitors (HHyPs), and highlighted signaling axes, such as Notch/TGF-β, WNT, and HGF, as key regulators of fate decisions. Importantly, non-parenchymal cells-including endothelial and stellate lineages-emerge as critical microenvironmental instructors, acting through ligand-receptor networks and spatial gradients. A new paradigm is thus emerging in which cell atlas construction, intercellular communication analysis, spatial validation, and organoid-based functional modeling form an iterative loop to decode developmental programs. Taken together, these insights mark a shift from descriptive cataloging to mechanistic dissection of liver organogenesis, providing a conceptual and methodological foundation for translational applications in congenital liver disease, tumor stratification, and regenerative medicine.