Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors

• DOI: 10.1038/s41467-019-11266-x
• Publication Date: 2019-07-26T10:03:04Z
• Authors: Joe M. Segal; Deniz Kent; Daniel J. Wesche; Soon Seng Ng; Maria Serra; Bénédicte Oulès; Gozde Kar; Guy Emerton; Samuel J. I. Blac...; Spyros Darmanis; Rosa Miquel; Tu Vinh Luong; Ryo Yamamoto; Andrew Bonham; Wayel Jassem; Nigel Heaton; Alessandra Vigilante; Aileen King; Rocio Sancho; Sarah Teichmann; Stephen R. Quake; Hiromitsu Nakauchi; S. Tamir Rashid
• Keywords: 0303 health sciences; Transcription, Genetic; Science; Stem Cells; Q; Epithelial Cell Adhesion Molecule; Article; 03 medical and health sciences; Fetus; Liver; Antigens, Neoplasm; 616; Hepatocytes; Humans; Single-Cell Analysis; Cell Adhesion Molecules

AbstractThe liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human foetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of foetal liver and maintain a transcriptional profile distinct from foetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogeneity within the EpCAM+population of freshly isolated foetal and adult human liver identifies diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolate foetal HHyPs and confirm their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles.