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 Heaton; Alessandra Vigilante; Rocio Sancho; Sarah A Teichmann

doi:10.1038/s41467-019-11266-x

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 language	English
Article number	3350
Number of pages	14
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11266-x
Publication status	Accepted/In press - 24 Jun 2019

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Single cell analysis of human_SEGAL_Accepted24June2019_GOLD AAMAccepted author manuscript, 66.6 MBLicence: CC BY
Single cell analysis of human foetal_VIGILANTE_Publishedonline26July2019_GOLD CORRECTED PROOF (CC BY)Proof, 8.66 MBLicence: CC BY

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Segal, J. M., Kent, D. H., Wesche, D., Ng, S. S., Quake, S., Serra, M., Nakauchi, H., Rashid, S. T., King, A., Oules, B., Kar, G., Emerton, G., Blackford, S., Darmanis, S., Miquel, R., Luong, T. V., Yamamoto, R., Bonham, A., Jassem, W., ... Teichmann, S. A. (Accepted/In press). Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors. Nature Communications, 10(1), [3350]. https://doi.org/10.1038/s41467-019-11266-x

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title = "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.",

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

year = "2019",

month = jun,

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doi = "10.1038/s41467-019-11266-x",

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Segal, JM , Kent, DH, Wesche, D, Ng, SS, Quake, S, Serra, M, Nakauchi, H, Rashid, ST , King, A , Oules, B, Kar, G, Emerton, G, Blackford, S, Darmanis, S, Miquel, R, Luong, TV, Yamamoto, R, Bonham, A, Jassem, W, Heaton, N, Vigilante, A , Sancho, R & Teichmann, SA 2019, 'Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors', Nature Communications, vol. 10, no. 1, 3350. https://doi.org/10.1038/s41467-019-11266-x

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T1 - Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors

AU - Segal, Joe Monty

AU - Kent, Deniz Haluk

AU - Wesche, Daniel

AU - Ng, Soon Seng

AU - Quake, Stephen

AU - Serra, Maria

AU - Nakauchi, Hiromitsu

AU - Rashid, Sheikh Tamir

AU - King, Aileen

AU - Oules, Benedicte

AU - Kar, Gozde

AU - Emerton, Guy

AU - Blackford, Samuel

AU - Darmanis, Spyros

AU - Miquel, Rosa

AU - Luong, Tu Vinh

AU - Yamamoto, Ryo

AU - Bonham, Andrew

AU - Jassem, Wayel

AU - Heaton, Nigel

AU - Vigilante, Alessandra

AU - Sancho, Rocio

AU - Teichmann, Sarah A

PY - 2019/6/24

Y1 - 2019/6/24

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-11266-x

DO - 10.1038/s41467-019-11266-x

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3350

ER -

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

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