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Single-cell atlas of human pediatric liver reveals age-related hepatic gene signatures.

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Τίτλος: Single-cell atlas of human pediatric liver reveals age-related hepatic gene signatures.
Συγγραφείς: Edgar RD; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.; Donnelly Centre, University of Toronto, Toronto, Ontario, Canada., Nakib D; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Camat D; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Chung S; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Lumanto P; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada., Atif J; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Perciani CT; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Ma XZ; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada., Thoeni C; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Selvakumaran N; Division of Gastroenterology, Hepatology & Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Manuel J; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada., Sayed B; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada., Huysentruyt K; Division of Gastroenterology, Hepatology & Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.; Brussels Centre for Intestinal Rehabilitation in Children, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium., Ricciuto A; Division of Gastroenterology, Hepatology & Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., McGilvray I; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada., Avitzur Y; Division of Gastroenterology, Hepatology & Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Bader GD; Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.; CIFAR Multiscale Human Program, CIFAR, Toronto, Ontario, Canada., MacParland SA; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Πηγή: Hepatology communications [Hepatol Commun] 2025 Oct 07; Vol. 9 (11). Date of Electronic Publication: 2025 Oct 07 (Print Publication: 2025).
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 101695860 Publication Model: eCollection Cited Medium: Internet ISSN: 2471-254X (Electronic) Linking ISSN: 2471254X NLM ISO Abbreviation: Hepatol Commun Subsets: MEDLINE
Imprint Name(s): Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc.
Original Publication: [Hoboken, NJ] : Wiley Periodicals, Inc. on behalf of the American Association for the Study of Liver Diseases, [2017]-
Ιατρικοί όροι (MeSH): Liver*/metabolism , Liver*/pathology , Liver*/cytology , Transcriptome*, Kupffer Cells/metabolism ; Humans ; Child ; Adult ; Single-Cell Analysis ; Adolescent ; Male ; Female ; Age Factors ; Middle Aged ; Child, Preschool ; Aged ; Infant
Περίληψη: Background: The liver plays a critical role in metabolism and immune function, yet the contributions of its heterogeneous cell types to these processes remain unclear. While most liver studies focus on adults, pediatric liver diseases often present differently, underscoring the need for age-specific research.
Methods: To better understand cellular drivers of childhood liver diseases, we generated single-cell RNA-sequencing maps of the normal pediatric liver and used this map to examine disease-related populations in biopsies from pediatric patients with intestinal failure-associated liver disease (IFALD).
Results: The normal pediatric liver map consists of 42,660 cells from 9 donors under 17 years of age. Compared with normal adult liver (26,372 cells; 7 donors, age 26-69), pediatric livers exhibited differences in myeloid populations. Specifically, pediatric Kupffer-like cells (MARCO+C1QA+VSIG4+) exhibited higher expression of immune activation genes, including CCL4, CCL3, and IL1B. In vitro stimulation confirmed more IL-1β-secreting myeloid cells in pediatric versus adult livers, supporting these findings. Using the pediatric atlas as a reference, we analyzed 3 IFALD biopsies (11,969 cells; 3 donors, under 9 y of age) and identified increased expression of fibrosis-associated genes (eg, LY96) in Kupffer-like cells. In addition, mesenchymal cells in IFALD showed fibrotic gene modules resembling adult liver cells more than healthy pediatric cells. These signatures, undetectable when comparing IFALD to adult liver alone, highlight the value of a pediatric map.
Conclusion: Taken together, our healthy pediatric liver atlas reveals distinct age-related signatures and provides a background against which to interpret pediatric liver disease data.
(Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
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Contributed Indexing: Keywords: HSCs; KC; liver zonation; single-cell transcriptomics; spatial transcriptomics
Molecular Sequence: GEO GSE286254
Entry Date(s): Date Created: 20251007 Date Completed: 20251007 Latest Revision: 20260915
Update Code: 20260916
PubMed Central ID: PMC12506995
DOI: 10.1097/HC9.0000000000000813
PMID: 41056487
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2471-254X
DOI:10.1097/HC9.0000000000000813