IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration
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Abstract
Although midlobular hepatocytes in zone 2 are a recently identified cellular source for liver homeostasis and regeneration, these cells have not been exclusively fate mapped. We generated an Igfbp2-CreER knockin strain that specifically labels midlobular hepatocytes. During homeostasis over 1 year, zone 2 hepatocytes increased in abundance from occupying 21%-41% of the lobular area. After either pericentral injury with carbon tetrachloride or periportal injury with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), IGFBP2+ cells replenished lost hepatocytes in zones 3 and 1, respectively. IGFBP2+ cells also preferentially contributed to regeneration after 70% partial hepatectomy, as well as liver growth during pregnancy. Because IGFBP2 labeling increased substantially with fasting, we used single nuclear transcriptomics to explore zonation as a function of nutrition, revealing that the zonal division of labor shifts dramatically with fasting. These studies demonstrate the contribution of IGFBP2-labeled zone 2 hepatocytes to liver homeostasis and regeneration.
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Zone 2 hepatocytes traced by Igfbp2-CreER proliferate more during regeneration after partial hepatectomy and during pregnancy, can replace zone 3 and 1 hepatocytes after CCl4- or DDC-induced injury, and their proliferation is nutritionally regulated.
“A recent study shows that zone 2 hepatocytes traced by Igfbp2-CreER proliferate more during regeneration after partial hepatectomy and during pregnancy. Additionally, they can replace zone 3 and 1 hepatocytes after CCl4- or DDC-induced injury, and their proliferation is nutritionally regulated136”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [136]
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Self-citationZonated mechanosensing by PIEZO1 controls liver regeneration
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Self-citation
- Authors
- Lin, Y.-H., Wei, Y., Zeng, Q., Wang, Y., Pagani, C. A., Li, L., Zhu, M., Wang, Z., Hsieh, M.-H., Corbitt, N., Zhang, Y., Sharma, T., Wang, T., & Zhu, H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Zhu, Hao
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2023-05
- Volume
- 30
- Issue
- 5
- Pages
- 665-676.e4
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC10580294
- OpenAlex
- W4368363439
- Cited by
- 33
- References
- 6
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 8 · 2023: 3
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- NIAAA
- National Cancer Institute (CA251928, R01CA258584)
- NIDDK (DK125396)
- Alnylam Pharmaceuticals
- Mark Foundation For Cancer Research (21-003-ELA)
- National Institutes of Health
- 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 › Tissue Engineering and Regenerative Medicine
- Keywords
- IGFBP-2, liver regeneration, liver homeostasis, partial hepatectomy, fasting, hepatocyte zonation
- MeSH terms
- Hepatectomy, Homeostasis, Liver, Liver Regeneration, Insulin-Like Growth Factor Binding Protein 2, Hepatocytes
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