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Single-cell atlas of human liver development reveals pathways directing hepatic cell fates

Lookup NU author(s): Dave Horsfall, Dr Rachel Botting, Emily Stephenson, Dr Dorin-Mirel Popescu, Professor Muzlifah Haniffa

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Abstract

© 2022, The Author(s), under exclusive licence to Springer Nature Limited.The liver has been studied extensively due to the broad number of diseases affecting its vital functions. However, therapeutic advances have been hampered by the lack of knowledge concerning human hepatic development. Here, we addressed this limitation by describing the developmental trajectories of different cell types that make up the human liver at single-cell resolution. These transcriptomic analyses revealed that sequential cell-to-cell interactions direct functional maturation of hepatocytes, with non-parenchymal cells playing essential roles during organogenesis. We utilized this information to derive bipotential hepatoblast organoids and then exploited this model system to validate the importance of signalling pathways in hepatocyte and cholangiocyte specification. Further insights into hepatic maturation also enabled the identification of stage-specific transcription factors to improve the functionality of hepatocyte-like cells generated from human pluripotent stem cells. Thus, our study establishes a platform to investigate the basic mechanisms directing human liver development and to produce cell types for clinical applications.

Publication metadata

Author(s): Wesley BT, Ross ADB, Muraro D, Miao Z, Saxton S, Tomaz RA, Morell CM, Ridley K, Zacharis ED, Petrus-Reurer S, Kraiczy J, Mahbubani KT, Brown S, Garcia-Bernardo J, Alsinet C, Gaffney D, Horsfall D, Tysoe OC, Botting RA, Stephenson E, Popescu D-M, MacParland S, Bader G, McGilvray ID, Ortmann D, Sampaziotis F, Saeb-Parsy K, Haniffa M, Stevens KR, Zilbauer M, Teichmann SA, Vallier L

Publication type: Article

Publication status: Published

Journal: Nature Cell Biology

Year: 2022

Volume: 24

Pages: 487–1498

Online publication date: 15/09/2022

Acceptance date: 29/07/2022

ISSN (print): 1465-7392

ISSN (electronic): 1476-4679

Publisher: Nature Research

URL: https://doi.org/10.1038/s41556-022-00989-7

DOI: 10.1038/s41556-022-00989-7

PubMed id: 36109670

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