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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Segal JM,Kent D,Wesche DJ,Ng SS,Serra M,Oulès B,Kar G,Emerton G,Blackford SJI,Darmanis S,Miquel R,Luong TV,Yamamoto R,Bonham A,Jassem W,Heaton N,Vigilante A,King A,Sancho R,Teichmann S,Quake SR,Nakauchi H,Rash

doi

10.1038/s41467-019-11266-x

subject

Has Abstract

pub_date

2019-07-26 00:00:00

pages

3350

issue

1

issn

2041-1723

pii

10.1038/s41467-019-11266-x

journal_volume

10

pub_type

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