The Conundrum of the Pericentral Hepatic Niche: WNT/-Catenin Signaling, Metabolic Zonation, and Many Open Questions
Open accessAbstract
WNT/-catenin signaling promotes stemness, proliferation, and cell fate decisions in various tissue stem cell compartments, which maintain organs with a high turnover of cells (e.g., skin, stomach, and gut). Thus, the -catenin target genes AXIN2 and LGR5 are widely considered as tissue stem cell markers. In contrast, AXIN2 and LGR5 are expressed in pericentral hepatocytes, which do not show overt proliferation during liver homeostasis. Given the low hepatocyte turnover, the liver does not require constant high rates of proliferation, whereas WNT/-catenin signaling is critical for metabolic zonation. Yet, WNT/-catenin pathway upregulation, including AXIN2 and LGR5 induction in hepatocytes throughout the liver, enables hepatocyte regeneration in response to various injuries. In this brief review, I discuss the role of WNT/-catenin signaling in controlling metabolic zonation and the conundrum around pericentral hepatocytes that have been proposed as liver stem cells.
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Since the same pathways that induce and maintain metabolic function also control hepatocyte proliferation, restricting unnecessary proliferation while maintaining the metabolic identity of hepatocytes in the different zones is an important balancing act for the liver.
“Since the same pathways that induce and maintain metabolic function also control hepatocyte proliferation, restricting unnecessary proliferation while maintaining the metabolic identity of hepatocytes in the different zones is an important balancing act for the liver.22,76”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [76]
Cites
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The RSPO–LGR4/5–ZNRF3/RNF43 module controls liver zonation and size
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Self-citationLiver zonation: Novel aspects of its regulation and its impact on homeostasis
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AXIN2+ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration
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The RSPO‐LGR4/5‐ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease
Annunziato, S., Sun, T., & Tchorz, J. S. (2022) · Hepatology · doi:10.1002/hep.32328 · Cited by 45 · see citing works
Self-citationDistinct hepatocyte identities in liver homeostasis and regeneration
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- Authors
- Tchorz, J. S.
- Affiliations
- Novartis (Switzerland) (CH)
- Corresponding author
- Tchorz, Jan S.
- ORCID
- Tchorz, Jan S.
- Venue
- Gene Expression
- Publisher
- Xia & He Publishing
- Published
- 2020-11-11
- Volume
- 20
- Issue
- 2
- Pages
- 119-124
- ISSN
- 1052-2166 (ISSN-L)
- PMC
- PMC7650010
- OpenAlex
- W3088195983
- Cited by
- 6
- References
- 9
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1
- FWCI
- 0.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Gene Expression (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- pericentral hepatocytes, liver stem cells, metabolic zonation, Axin2, Lgr5, hepatocyte regeneration, liver homeostasis, hepatocyte proliferation, liver injury
- MeSH terms
- Animals, Humans, Liver, Liver Regeneration, Stem Cell Niche, Wnt Signaling Pathway
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