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

Joe Monty Segal, Deniz Haluk Kent, Daniel Wesche, Soon Seng Ng, Stephen Quake, Maria Serra, Hiromitsu Nakauchi, Sheikh Tamir Rashid, Aileen King, Benedicte Oules, Gozde Kar, Guy Emerton, Samuel Blackford, Spyros Darmanis, Rosa Miquel, Tu Vinh Luong, Ryo Yamamoto, Andrew Bonham, Wayel Jassem, Nigel HeatonAlessandra Vigilante, Rocio Sancho, Sarah A Teichmann

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Abstract

The 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.
Original languageEnglish
Article number3350
Number of pages14
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusAccepted/In press - 24 Jun 2019

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