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Towards a reference cell atlas of liver diversity over the human lifespan

Nature Reviews Gastroenterology & Hepatology volume 23, pages 97–109 (2026)Cite this article

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An Author Correction to this article was published on 23 October 2025

This article has been updated

Abstract

The goal of the Human Liver Cell Atlas (HLiCA) is to create a comprehensive map that defines the normal functions of diverse liver cell types and their spatial relationships over the human lifespan. This project fits within the goals of the Human Cell Atlas to create comprehensive reference maps of all human cells as a basis for both understanding human health and diagnosing, monitoring and treating disease. Through collection of samples from diverse individuals, data integration across technologies and overcoming liver-specific challenges for experimental methods, the HLiCA will map as many cell types and states as possible in healthy human livers from individuals across all ages and many ancestries. Establishing this HLiCA of healthy livers is a critical step to begin to understand perturbations in disease. The HLiCA will be available on an open-access platform to facilitate data sharing and dissemination. We expect that creation of the HLiCA will help to lay the foundation for new research initiatives to advance our understanding of liver disease, improve methods of tissue engineering, and identify novel prognostic biomarkers and therapies to improve patient outcomes. We describe key experimental and computational challenges to overcome in building the atlas and the potential impact of the atlas on disease research.

Key points

  • Building the Human Liver Cell Atlas requires collaborative effort within the liver single-cell genomics community.

  • Characterization of the normal human liver must account for sample-to-sample variability due to age, gender, ancestry, lifestyle, microbiome, environmental factors and experimental approaches, among other factors.

  • Collecting standardized metadata and optimizing data integration is critical to generate a useful and comprehensive cell atlas across multiple laboratories and institutions.

  • The Human Liver Cell Atlas will provide the foundation for understanding disease-specific perturbations and hopefully identify cell-type-specific therapeutic strategies to reduce the global burden of liver disease.

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Fig. 1: Overview of human liver anatomy.
Fig. 2: Methods for single-cell analyses to build an atlas for healthy human liver cells.
Fig. 3: Proposed metadata to generate a comprehensive liver cell atlas.
Fig. 4: Single-cell technology can help to improve outcomes in human liver disease.

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Acknowledgements

The authors thank F. Hamade, biomedical illustrator, for creating the initial draft of the figures. They thank the HCA executive office, data portal and Lattice staff for outstanding project support. The HLiCA project is supported by funding from the Chan Zuckerberg Initiative (to S. A. Taylor, G.D.B., S.M., A.C.M., A.G.C., R.D., D.G., M.G., N.C.H., S.S.H., S.I., G.M.L., I.M., K.R.M., G.Q., A. Regev, A. Ricciuto, C.L.S., M.M.T., S. A. Teichmann, L.V., B.W. and M.Z.). Additional support was provided by the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K08 grant DK121937 (to S. A. Taylor); NSERC Discovery grant RGPIN-2023-03419 and CIHR grant RN482632-481311 (to T.A.); CIHR grant PJT 180542 (to G.D.B.); CZI Seed Network grant CZIF2019-002429, Singapore National Medical Research Council (NMRC) grants NMRC/TCR/14-NUHS/2015 and NMRC/OFLCG19May-0038, and National Research Foundation grant (NRF-CRP) CRP26-2021-0005 (to R.D.); the Bundesministerium für Bildung und Forschung (BMBF) CureFib – 01EJ2201C (to D.G.); Ghent University BOF18-GOA-024 and BOF24/GOA/035 and FWO project grants 3G000519 and G013823N (to M.G.); Wellcome Trust Senior Research Fellowship in Clinical Science (ref. 219542/Z/19/Z) and the Medical Research Council (N.C.H.); R01DK132751 and R01DK120765 (S.S.H.); Helen and Martin Kimmel Award for Innovative Investigation, the Yad Abraham Research Center for Cancer Diagnostics and Therapy, the Moross Integrated Cancer Center, the Minerva Stiftung grant, a Weizmann-Sheba grant, the Israel Science Foundation grants no. 908/21 and 3663/21, the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme grant no. 768956 and a grant from the Ministry of Innovation, Science & Technology, Israel (to S.I.); Massachusetts Life Science Center (MLSC) and NIH grants R01AA030770 and K08 DK115883 (to Z.G.J); the ERC (MyeFattyLiver no. 851908) and FWO project grants 3G000519, G075923N and G0A9Z24N (to C.L.S.); CSL Centenary Fellowship and National Health and Medical Research Council (NHMRC) Ideas Grant 2021/GNT2010795 (to A.S.); NIDDK R21 grant DK127275-01 (to M.M.T.); Advanced grant NewChol (to L.V.); NHLBI U54 HL 165440-01 grant (to I.S.V.); Hector Foundation, Dieter Morszeck Foundation and the German Research Foundation (SFB 1479) (to M.R.).

Author information

Author notes

  1. Aviv Regev

    Present address: Genentech, South San Francisco, CA, USA

Authors and Affiliations

  1. Department of Pediatrics, Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA

    Sarah A. Taylor

  2. The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada

    Gary D. Bader

  3. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

    Gary D. Bader & Mei Zhen

  4. Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

    Sonya MacParland & Ian McGilvray

  5. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    Sonya MacParland

  6. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Sonya MacParland

  7. Division of Gastroenterology, University of Massachusetts Chan Medical School, Worcester, MA, USA

    Alan C. Mullen

  8. Broad Institute, Cambridge, MA, USA

    Alan C. Mullen, Aviv Regev & Ioannis S. Vlachos

  9. Department of Biochemistry, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada

    Tallulah Andrews

  10. Department of Computer Science, University of Western Ontario, London, Ontario, Canada

    Tallulah Andrews

  11. Department of Oncology, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada

    Tallulah Andrews

  12. Department of Surgery, Boston Children’s Hospital, Boston, MA, USA

    Alex G. Cuenca

  13. Laboratory of Tumour Evolution, University of Glasgow, Glasgow, UK

    Ramanuj DasGupta

  14. Precision Oncology, School of Cancer Sciences, University of Glasgow, Glasgow, UK

    Ramanuj DasGupta

  15. CRUK Scotland Institute, Glasgow, UK

    Ramanuj DasGupta

  16. Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada

    Adam J. Gehring, Aliya Gulamhusein & Gideon Hirschfield

  17. Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg, Würzburg, Germany

    Dominic Grün

  18. Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB Center for Inflammation Research, Ghent, Belgium

    Martin Guilliams

  19. Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium

    Martin Guilliams & Charlotte L. Scott

  20. Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK

    Neil C. Henderson

  21. MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK

    Neil C. Henderson

  22. Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Stacey S. Huppert

  23. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Stacey S. Huppert

  24. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

    Shalev Itzkovitz

  25. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Z. Gordon Jiang

  26. Liver Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Georg M. Lauer

  27. Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA

    Krupa R. Mysore

  28. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    Carlos J. Pirola & Silvia Sookoian

  29. Systems Biology of Complex Diseases, Translational Research in Health Center (CENITRES), Maimónides University, Buenos Aires, Argentina

    Carlos J. Pirola

  30. Department of Molecular and Cellular Biology, University of California, Davis, CA, USA

    Gerald Quon

  31. Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Mohammad Rahbari

  32. Department of Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

    Mohammad Rahbari

  33. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada

    Amanda Ricciuto

  34. Laboratory of Myeloid Cell Biology in Tissue Injury and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium

    Charlotte L. Scott

  35. Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia

    Ankur Sharma

  36. Clinical and Molecular Hepatology, Translational Research in Health Center (CENITRES), Maimónides University, Buenos Aires, Argentina

    Silvia Sookoian

  37. Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, CA, USA

    Michele M. Tana

  38. UCSF Liver Center, San Francisco, CA, USA

    Michele M. Tana

  39. Department of Medicine, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK

    Sarah A. Teichmann

  40. Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK

    Sarah A. Teichmann

  41. BIH Center for Regenerative Therapies, Berlin Institute of Health at Charité, Berlin, Germany

    Ludovic Vallier

  42. Max Planck Institute for Molecular Genetics, Berlin, Germany

    Ludovic Vallier

  43. Spatial Technologies Unit, Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA

    Ioannis S. Vlachos

  44. Harvard Medical School, Boston, MA, USA

    Ioannis S. Vlachos

  45. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Ioannis S. Vlachos

  46. Department of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA

    Bruce Wang

  47. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

    Mei Zhen

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Contributions

The authors contributed equally to writing and reviewing/editing the manuscript before submission. S. A. Taylor, G.D.B., S.M. and A.C.M. researched data for the article and contributed substantially to discussion of the content.

Corresponding authors

Correspondence to Gary D. Bader or Alan C. Mullen.

Ethics declarations

Competing interests

S. A. Taylor serves as a consultant for Ipsen Pharmaceutical. A.C.M. receives funding from GSK and Boehringer Ingelheim for unrelated projects. A.J.G. receives research funding from Aligos Therapeutics, Bluejay Therapeutics, GSK, Roche and Vir Biotechnology, and performs scientific advisory services for Aligos Therapeutics, Arbutus Biopharma, Assembly Biosciences, Bluejay Therapeutics, Gilead Sciences, GSK, Janssen Pharmaceuticals, Roche, Vir Biotechnology, Virion Therapeutics and VBI for unrelated projects. D.G. serves as a consultant for Gordian Biotechnology. M.G. receives funding from the Sanofi iTech Award programme for an unrelated project. N.C.H. has received research funding from AbbVie, Pfizer, Gilead and Boehringer-Ingelheim, and is an adviser or consultant for Astra-Zeneca, GSK and MSD. S.S.H serves as a consultant for ARNATAR Therapeutics. Z.G.J. serves on the advisory board of Olix Pharmaceuticals, and received grants from Pfizer and Gilead Sciences. A. Ricciuto receives a stipend for academic lectures from Janssen and Organon. C.L.S. receives funding from Novo Nordisk for unrelated projects. M.M.T has served as a consultant for Merck for an unrelated project. L.V. is a shareholder of Definigen, BiliTech and Bit.bio. I.S.V. consults for Guidepoint Global, Cowen and Mosaic. B.W. serves as a consultant for Alnylam Pharmaceuticals, Disc Medicine, Mitsubishi Tanabe Pharma and Recordati Rare Diseases. G.D.B. advises Adela Bio and BioRender. The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks the anonymous reviewers for their contribution to the peer review of this work.

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Related links

Cell Annotation Platform: https://celltype.info

CellMarker: http://117.50.127.228/CellMarker

CELL×GENE: https://cellxgene.cziscience.com

HCA community: https://www.humancellatlas.org/join-the-hca

Human Cell Atlas: https://www.humancellatlas.org

Human Liver Cell Atlas: https://www.humancellatlas.org/biological-networks/liver-biological-network

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Taylor, S.A., Bader, G.D., MacParland, S. et al. Towards a reference cell atlas of liver diversity over the human lifespan. Nat Rev Gastroenterol Hepatol 23, 97–109 (2026). https://doi.org/10.1038/s41575-025-01114-3

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