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

## TL;DR

This study creates a detailed cell atlas of liver organoids and compares them to fetal liver tissue to understand development and improve culture methods.

## Contribution

The paper introduces a unified single-cell RNA-seq atlas of liver organoids across multiple culture protocols and compares them to fetal liver data.

## Key findings

- Liver organoids show diverse cellular compositions depending on culture conditions.
- Organoids lack representation of hematopoietic lineages compared to fetal liver tissue.
- NOTCH, VEGF, HGF, and WNT signaling are prominent in liver organoids.

## Abstract

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.

•Single-cell transcriptomic atlas of liver organoids was constructed across culture protocols•A systematic comparison was performed among protocols and between organoids and fetal liver•Cell trajectory and communication were analyzed to guide culture system optimization

Single-cell transcriptomic atlas of liver organoids was constructed across culture protocols

A systematic comparison was performed among protocols and between organoids and fetal liver

Cell trajectory and communication were analyzed to guide culture system optimization

Medicine; Integrative aspects of cell biology; Transcriptomics