SINGLE-CELL RNA-SEQ DECIPHERS ENDODERMAL ORIGIN AND LIVER DEVELOPMENT BY TRACING FOXA2 LINEAGE

Abstract

Using a transgenic Foxa2-EGFP reporter mouse line, we here performed deep single-cell RNA sequencing on 1,966 individual cells isolated from the endoderm and hepatic regions from ten embryonic stages, ranging from day E7.5 to E15.5. We identified the embryonic liver developmental trajectory from the primitive streak to hepatoblasts and characterized the transcriptome of the hepatic lineage. During the liver specification stages, liver primordium was identified to share both the foregut and liver features. We have documented dynamic gene expression during the epithelial-hepatic transition (EHT). Six gene groups were found to switch on or off during liver specification. Importantly, we found that RXR complex signaling and newly identified transcription factors associated with liver specification. The present data provides a high-resolution resource and critical insights for understanding the emergence of the endoderm, liver and gall bladder development.