Progressive fibrosis in human MASLD is associated with spatially linked transcriptomic signatures of metabolic reprogramming and senescence
Metabolic dysfunction-associated steatotic liver disease (MASLD) has a complex pathogenesis driven by cell and matrix interactions in inflammatory niches. In this study, we identify a senescence signature in fibroinflammatory regions, characterised by high immunoglobulin expression and associated with a shift from oxidative to glycolytic metabolism. We identify spatially co-expressed ligand-receptor pairs, including senescence-associated factors, correlated with progressive fibrosis. This discovery dataset highlights the complex crosstalk between metabolic perturbations and inflammation underpinning fibrosis progression in MASLD and lays the groundwork for future research into the role of senescence in MASLD.
Authors
- Yuliangzi Sun (ORCID: https://orcid.org/0000-0001-9785-4261)
- Andrew Causer (ORCID: https://orcid.org/0009-0001-7341-8366)
- Zherui Xiong (ORCID: https://orcid.org/0000-0002-5038-5629)
- Matthew J. Watt (ORCID: https://orcid.org/0000-0003-4064-4188)
- Christian M. Nefzger (ORCID: https://orcid.org/0000-0003-4631-5633)
- Alex M. Dickens (ORCID: https://orcid.org/0000-0002-3178-8449)
- Grant A. Ramm (ORCID: https://orcid.org/0000-0001-7058-6201)
- Xiao Tan (ORCID: https://orcid.org/0000-0001-9210-439X)
- Elizabeth E. Powell (ORCID: https://orcid.org/0000-0001-5008-8061)
- Quan Nguyen (ORCID: https://orcid.org/0000-0001-7870-5703)
- Katharine M. Irvine (ORCID: https://orcid.org/0000-0002-6716-1605)
- Andrew D. Clouston (ORCID: https://orcid.org/0000-0002-9601-7952)
- Daniel Radford‐Smith (ORCID: https://orcid.org/0000-0001-8781-7459)
- Matej Orešič (ORCID: https://orcid.org/0000-0002-2856-9165)
- Tuulia Hyötyläinen (ORCID: https://orcid.org/0000-0002-4382-4355)
- Eoin O’Sullivan (ORCID: https://orcid.org/0000-0002-7709-6595)
- Hani Vu (ORCID: https://orcid.org/0009-0002-4337-366X)
- Ilia Evstafev (ORCID: https://orcid.org/0009-0007-9232-9418)
Institutions
- Åbo Akademi University (FI)
- Translational Research Institute (AU)
- University of Turku (FI)
- The University of Queensland (AU)
- The University of Melbourne (AU)
- Turku Centre for Computer Science (FI)
- QIMR Berghofer Medical Research Institute (AU)
- Örebro University (SE)
- Princess Alexandra Hospital (AU)
- University of Oxford (GB)
- Metro South Health (AU)
- Mater Research (AU)
- Kidney Health Australia (AU)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101657
- Citations
- 1
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.35