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

Author

Listed:
  • Joe M. Segal

    (King’s College London)

  • Deniz Kent

    (King’s College London)

  • Daniel J. Wesche

    (Stanford University School of Medicine
    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
    Stanford University School of Medicine)

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.

Suggested Citation

  • 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 Yam, 2019. "Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11266-x
    DOI: 10.1038/s41467-019-11266-x
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    Cited by:

    1. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Delilah Hendriks & Benedetta Artegiani & Thanasis Margaritis & Iris Zoutendijk & Susana Chuva de Sousa Lopes & Hans Clevers, 2024. "Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Jie Fang & Shivendra Singh & Changde Cheng & Sivaraman Natarajan & Heather Sheppard & Ahmed Abu-Zaid & Adam D. Durbin & Ha Won Lee & Qiong Wu & Jacob Steele & Jon P. Connelly & Hongjian Jin & Wenan Ch, 2023. "Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma," Nature Communications, Nature, vol. 14(1), pages 1-27, December.

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