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

Research output: Contribution to journalArticle

Joe Monty Segal, Deniz Haluk Kent, Daniel Wesche, Soon Seng Ng, Stephen Quake, Hiromitsu Nakauchi, Sheikh Tamir Rashid

Original languageEnglish
JournalNature Communications
Publication statusAccepted/In press - 24 Jun 2019

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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 heterogenicity 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.

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