A cell atlas of multiple liver organoids and the fetal liver based on scRNA-seq.

Understanding the cellular characteristics and regulatory networks of cells during the growth of human liver organoids is crucial for comprehending liver development and function. However, a comprehensive cell atlas of liver organoids spanning multiple culture protocols is still lacking. To address this gap, we integrated scRNA-seq datasets of liver organoids from public repositories with published human fetal liver datasets, constructing a unified liver organoid cell atlas comprising 217,025 high-quality cells. This atlas captures diverse cellular compositions across culture conditions of liver organoids. Comparative analyses revealed deficiencies in hematopoietic lineage representation in organoids relative to fetal tissues. Subpopulation and pseudotime analyses provided insights into hepatoblast fate transitions, while cell-cell communication analysis highlighted prominent NOTCH, VEGF, HGF, and WNT signaling activities in organoids. Together, our study delineates differences between liver organoids and fetal tissues and enables systematic comparison across culture protocols, providing a framework for protocol evaluation and optimization.