Mfsd2a+ hepatocytes repopulate the liver during injury and regeneration
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Abstract Hepatocytes are functionally heterogeneous and are divided into two distinct populations based on their metabolic zonation: the periportal and pericentral hepatocytes. During liver injury and regeneration, the cellular dynamics of these two distinct populations remain largely elusive. Here we show that major facilitator super family domain containing 2a (Mfsd2a), previously known to maintain blood–brain barrier function, is a periportal zonation marker. By genetic lineage tracing of Mfsd2a + periportal hepatocytes, we show that Mfsd2a + population decreases during liver homeostasis. Nevertheless, liver regeneration induced by partial hepatectomy significantly stimulates expansion of the Mfsd2a + periportal hepatocytes. Similarly, during chronic liver injury, the Mfsd2a + hepatocyte population expands and completely replaces the pericentral hepatocyte population throughout the whole liver. After injury recovery, the adult liver re-establishes the metabolic zonation by reprogramming the Mfsd2a + -derived hepatocytes into pericentral hepatocytes. The evidence of entire zonation replacement during injury increases our understanding of liver biology and disease.
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Periportal hepatocytes do not expand towards zone 3 under homeostatic conditions, and may reduce over time.
“Alternative methods based on tracing of periportal hepatocytes showed that periportal hepatocytes do not expand towards zone 360 under homeostatic conditions, and may reduce over time.84”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [84]
Lineage-tracing data have shown that hepatocytes in different zones can adopt the gene expression programme of the new zone they reside in.
“Additionally, lineage-tracing data have shown that hepatocytes in the different zones can adopt the gene expression programme of the new zone they reside in.49,60,84,86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [84]
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- Authors
- Pu, W., Zhang, H., Huang, X., Tian, X., He, L., Wang, Y., Zhang, L., Liu, Q., Li, Y., Li, Y., Zhao, H., Liu, K., Lu, J., Zhou, Y., Huang, P., Nie, Y., Yan, Y., Hui, L., Lui, K. O., & Zhou, B.
- Affiliations
- Chinese Academy of Sciences (CN)
- Tongji University (CN)
- ShanghaiTech University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Chinese University of Hong Kong (HK)
- Jinan University (CN)
- Corresponding author
- Zhou, Bin
- ORCID
- Venue
- Nature Communications
- Published
- 2016-11-18
- Volume
- 7
- Issue
- 1
- Pages
- 13369-13369
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5120209
- OpenAlex
- W2551147770
- Cited by
- 136
- References
- 5
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 18 · 2023: 17 · 2022: 12 · 2021: 16 · 2020: 18 · 2019: 9 · 2018: 11 · 2017: 7 · 2016: 1
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- AstraZeneca
- Sanofi
- National Natural Science Foundation of China (31625019, 81300340, CFHPC20131011, 31571503, 91339104, 31271552, 31222038, 31301188, 31571503, XDB19000000, 31501172, 31601168, 31271552, ZJ2014-ZD-002)
- Chinese Academy of Sciences (QYZDB-SSW-SMC003, 2015218, XDB19000000)
- China Postdoctoral Science Foundation (2013M541561, 2015M570389, 2016LH0042)
- Chinese Foundation for Hepatitis Prevention and Control (81300340)
- Directorate for Biological Sciences
- Health and Medical Research Fund (03140346)
- Youth Innovation Promotion Association (2015218)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- MFSD2A, hepatocytes, liver regeneration, liver injury, metabolic zonation, periportal hepatocytes, pericentral hepatocytes, lineage tracing, partial hepatectomy, chronic liver injury, hepatocyte heterogeneity
- MeSH terms
- Animals, Liver, Liver Regeneration, Cell Lineage, Hepatocytes, Membrane Transport Proteins, Symporters, Cell Proliferation, Mice
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