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

Joe M. Segal (), Deniz Kent, Daniel J. Wesche, Soon Seng Ng, Maria Serra, Bénédicte Oulès, Gozde Kar, Guy Emerton, Samuel J. I. Blackford, 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 and S. Tamir Rashid ()
Additional contact information
Joe M. Segal: King’s College London
Deniz Kent: King’s College London
Daniel J. Wesche: Stanford University School of Medicine
Soon Seng Ng: King’s College London
Maria Serra: King’s College London
Bénédicte Oulès: King’s College London
Gozde Kar: Wellcome Trust Sanger Institute
Guy Emerton: Wellcome Trust Sanger Institute
Samuel J. I. Blackford: King’s College London
Spyros Darmanis: Stanford University
Rosa Miquel: King’s College London
Tu Vinh Luong: King’s College London
Ryo Yamamoto: Stanford University School of Medicine
Andrew Bonham: Stanford University School of Medicine
Wayel Jassem: Kings College Hospital
Nigel Heaton: Kings College Hospital
Alessandra Vigilante: King’s College London
Aileen King: King’s College London
Rocio Sancho: King’s College London
Sarah Teichmann: Wellcome Trust Sanger Institute
Stephen R. Quake: Stanford University
Hiromitsu Nakauchi: Stanford University School of Medicine
S. Tamir Rashid: King’s College London

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11266-x

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