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

Sarah A Taylor¹, Gary D Bader^{2

3}, Sonya MacParland^{4

5

6}, Alan C Mullen^{7

8}, Tallulah Andrews^{9

10

11}, Alex G Cuenca¹², Ramanuj DasGupta^{13

14

15}, Adam J Gehring¹⁶, Dominic Grün¹⁷, Martin Guilliams^{18

19}, Aliya Gulamhusein¹⁶, Neil C Henderson^{20

21}, Gideon Hirschfield¹⁶, Stacey S Huppert^{22

23}, Shalev Itzkovitz²⁴, Z Gordon Jiang²⁵, Georg M Lauer²⁶, Ian McGilvray⁴, Krupa R Mysore²⁷, Carlos J Pirola^{28

29}, Gerald Quon³⁰, Mohammad Rahbari^{31

32}, Aviv Regev^{33

34}, Amanda Ricciuto³⁵, Charlotte L Scott^{19

36}, Ankur Sharma³⁷, Silvia Sookoian^{28

38}, Michele M Tana^{39

40}, Sarah A Teichmann^{41

42}, Ludovic Vallier^{43

44}, Ioannis S Vlachos^{33

45

46

47}, Bruce Wang⁴⁸, Mei Zhen^{49

50}

Affiliations

¹ Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
² The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. gary.bader@utoronto.ca.
³ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. gary.bader@utoronto.ca.
⁴ Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
⁵ Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁷ Division of Gastroenterology, University of Massachusetts Chan Medical School, Worcester, MA, USA. alan.mullen@umassmed.edu.
⁸ Broad Institute, Cambridge, MA, USA. alan.mullen@umassmed.edu.
⁹ Department of Biochemistry, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada.
¹⁰ Department of Computer Science, University of Western Ontario, London, Ontario, Canada.
¹¹ Department of Oncology, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada.
¹² Department of Surgery, Boston Children's Hospital, Boston, MA, USA.
¹³ Laboratory of Tumour Evolution, University of Glasgow, Glasgow, UK.
¹⁴ Precision Oncology, School of Cancer Sciences, University of Glasgow, Glasgow, UK.
¹⁵ CRUK Scotland Institute, Glasgow, UK.
¹⁶ Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.
¹⁷ Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
¹⁸ Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB Center for Inflammation Research, Ghent, Belgium.
¹⁹ Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium.
²⁰ Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
²¹ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
²² Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²³ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²⁴ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
²⁵ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
²⁶ Liver Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁷ Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
²⁸ Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
²⁹ Systems Biology of Complex Diseases, Translational Research in Health Center (CENITRES), Maimónides University, Buenos Aires, Argentina.
³⁰ Department of Molecular and Cellular Biology, University of California, Davis, CA, USA.
³¹ Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³² Department of Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
³³ Broad Institute, Cambridge, MA, USA.
³⁴ Genentech, South San Francisco, CA, USA.
³⁵ Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
³⁶ Laboratory of Myeloid Cell Biology in Tissue Injury and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
³⁷ Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
³⁸ Clinical and Molecular Hepatology, Translational Research in Health Center (CENITRES), Maimónides University, Buenos Aires, Argentina.
³⁹ Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, CA, USA.
⁴⁰ UCSF Liver Center, San Francisco, CA, USA.
⁴¹ Department of Medicine, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
⁴² Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
⁴³ BIH Center for Regenerative Therapies, Berlin Institute of Health at Charité, Berlin, Germany.
⁴⁴ Max Planck Institute for Molecular Genetics, Berlin, Germany.
⁴⁵ Spatial Technologies Unit, Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA.
⁴⁶ Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁴⁸ Department of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA.
⁴⁹ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁵⁰ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

PMID: 41083606
DOI: 10.1038/s41575-025-01114-3

Review

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

Sarah A Taylor et al. Nat Rev Gastroenterol Hepatol. 2025.

. 2025 Oct 13.

doi: 10.1038/s41575-025-01114-3. Online ahead of print.

Authors

Affiliations

¹ Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
² The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. gary.bader@utoronto.ca.
³ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. gary.bader@utoronto.ca.
⁴ Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
⁵ Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁷ Division of Gastroenterology, University of Massachusetts Chan Medical School, Worcester, MA, USA. alan.mullen@umassmed.edu.
⁸ Broad Institute, Cambridge, MA, USA. alan.mullen@umassmed.edu.
⁹ Department of Biochemistry, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada.
¹⁰ Department of Computer Science, University of Western Ontario, London, Ontario, Canada.
¹¹ Department of Oncology, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada.
¹² Department of Surgery, Boston Children's Hospital, Boston, MA, USA.
¹³ Laboratory of Tumour Evolution, University of Glasgow, Glasgow, UK.
¹⁴ Precision Oncology, School of Cancer Sciences, University of Glasgow, Glasgow, UK.
¹⁵ CRUK Scotland Institute, Glasgow, UK.
¹⁶ Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.
¹⁷ Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
¹⁸ Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB Center for Inflammation Research, Ghent, Belgium.
¹⁹ Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium.
²⁰ Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
²¹ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
²² Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²³ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²⁴ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
²⁵ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
²⁶ Liver Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁷ Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
²⁸ Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
²⁹ Systems Biology of Complex Diseases, Translational Research in Health Center (CENITRES), Maimónides University, Buenos Aires, Argentina.
³⁰ Department of Molecular and Cellular Biology, University of California, Davis, CA, USA.
³¹ Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³² Department of Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
³³ Broad Institute, Cambridge, MA, USA.
³⁴ Genentech, South San Francisco, CA, USA.
³⁵ Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
³⁶ Laboratory of Myeloid Cell Biology in Tissue Injury and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
³⁷ Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
³⁸ Clinical and Molecular Hepatology, Translational Research in Health Center (CENITRES), Maimónides University, Buenos Aires, Argentina.
³⁹ Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, CA, USA.
⁴⁰ UCSF Liver Center, San Francisco, CA, USA.
⁴¹ Department of Medicine, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
⁴² Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
⁴³ BIH Center for Regenerative Therapies, Berlin Institute of Health at Charité, Berlin, Germany.
⁴⁴ Max Planck Institute for Molecular Genetics, Berlin, Germany.
⁴⁵ Spatial Technologies Unit, Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA.
⁴⁶ Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁴⁸ Department of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA.
⁴⁹ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁵⁰ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

PMID: 41083606
DOI: 10.1038/s41575-025-01114-3

Erratum in

Author Correction: Towards a reference cell atlas of liver diversity over the human lifespan.
Taylor SA, Bader GD, MacParland S, Mullen AC, Andrews T, Cuenca AG, DasGupta R, Gehring AJ, Grün D, Guilliams M, Gulamhusein A, Henderson NC, Hirschfield G, Huppert SS, Itzkovitz S, Jiang ZG, Lauer GM, McGilvray I, Mysore KR, Pirola CJ, Quon G, Rahbari M, Regev A, Ricciuto A, Scott CL, Sharma A, Sookoian S, Tana MM, Teichmann SA, Vallier L, Vlachos IS, Wang B, Zhen M. Taylor SA, et al. Nat Rev Gastroenterol Hepatol. 2025 Oct 23. doi: 10.1038/s41575-025-01145-w. Online ahead of print. Nat Rev Gastroenterol Hepatol. 2025. PMID: 41131357 No abstract available.

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.

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Conflict of interest statement

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

Publication types

LinkOut - more resources

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