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

Autor:	Wesley BT; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Ross ADB; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK.; Department of Paediatrics, University of Cambridge, Cambridge, UK., Muraro D; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK.; Wellcome Sanger Institute, Hinxton, UK., Miao Z; Wellcome Sanger Institute, Hinxton, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK., Saxton S; Departments of Bioengineering and Pathology, University of Washington, Seattle, WA, USA.; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA., Tomaz RA; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Morell CM; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Ridley K; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Paediatrics, University of Cambridge, Cambridge, UK., Zacharis ED; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Petrus-Reurer S; Department of Surgery, University of Cambridge, Cambridge, UK.; NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Kraiczy J; Department of Paediatrics, University of Cambridge, Cambridge, UK., Mahbubani KT; Department of Surgery, University of Cambridge, Cambridge, UK., Brown S; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Garcia-Bernardo J; Wellcome Sanger Institute, Hinxton, UK., Alsinet C; Wellcome Sanger Institute, Hinxton, UK., Gaffney D; Wellcome Sanger Institute, Hinxton, UK., Horsfall D; Digital Institute, Newcastle University, Newcastle upon Tyne, UK., Tysoe OC; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Botting RA; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Stephenson E; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Popescu DM; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., MacParland S; University of Toronto, Toronto, Ontario, Canada., Bader G; University of Toronto, Toronto, Ontario, Canada., McGilvray ID; Multi-Organ Transplant Program, Toronto General Hospital Research Institute, Toronto, Ontario, Canada., Ortmann D; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Sampaziotis F; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Saeb-Parsy K; Department of Surgery, University of Cambridge, Cambridge, UK.; NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Haniffa M; Wellcome Sanger Institute, Hinxton, UK.; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Stevens KR; Departments of Bioengineering and Pathology, University of Washington, Seattle, WA, USA.; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA., Zilbauer M; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Paediatrics, University of Cambridge, Cambridge, UK., Teichmann SA; Wellcome Sanger Institute, Hinxton, UK.; Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, Cambridge, UK., Vallier L; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. lv225@cam.ac.uk.; Department of Surgery, University of Cambridge, Cambridge, UK. lv225@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Nature cell biology [Nat Cell Biol] 2022 Oct; Vol. 24 (10), pp. 1487-1498. Date of Electronic Publication: 2022 Sep 15.
DOI:	10.1038/s41556-022-00989-7
Abstrakt:	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. (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze:	MEDLINE
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