Mature hepatocytes are the source of small hepatocyte-like progenitor cells in the retrorsine model of liver injury
Abstract
Background/aims Mature hepatocytes divide to restore liver mass after injury. However, when hepatocyte division is impaired by retrorsine poisoning, regeneration proceeds from another cell type: the small hepatocyte-like progenitor cells (SHPCs). Our aim was to test whether SHPCs could originate from mature hepatocytes. Methods Mature hepatocytes were genetically labeled using retroviral vectors harboring the beta-galactosidase gene. After labeling, retrorsine was administered to rats followed by a partial hepatectomy to trigger regeneration. A liver biopsy was performed one month after surgery and rats were sacrificed one month later. Results We observed the proliferation of small hepatocytes arranged in clusters in liver biopsies. These cells expressed Ki67 antigen and displayed a high mitotic index. At sacrifice, regeneration was completed and clusters had merged. A significant proportion of clusters also expressed beta-galactosidase demonstrating their origin from labeled mature hepatocytes. Finally, the overall proportion of beta-galactosidase positive cells was identical at the time of hepatectomy as well as in liver biopsy and at sacrifice. Conclusions The constant proportion of beta-galactosidase positive cells during the regeneration process demonstrates that mature hepatocytes are randomly recruited to proliferate and compensate parenchyma loss in this model. Furthermore, mature hepatocytes are the source of SHPC after retrorsine injury.
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Hepatocytes are the source of small hepatocytes.
“a number of different approaches demonstrated that hepatocytes are the source of small hepatocytes.[143], [144], [145], [146]”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [145]
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- Authors
- Avril, A., Pichard, V., Bralet, M.-P., & Ferry, N.
- Affiliations
- Inserm (FR)
- Hôpital Paul-Brousse (FR)
- Corresponding author
- Ferry, Nicolas
- ORCID
- Pichard, Virginie
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 41
- Issue
- 5
- Pages
- 737-743
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2168649560
- Semantic Scholar
- 9e163cac36d5b25f897b0231356eb1ce066943bb
- Cited by
- 62
- References
- 46
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- 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
- liver regeneration, hepatocyte proliferation, partial hepatectomy, Ki-67, liver injury
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, beta-Galactosidase, Disease Models, Animal, Lac Operon, Liver Diseases, Liver Regeneration, Male, Pyrrolizidine Alkaloids, Stem Cells, Rats, Sprague-Dawley, Hepatocytes, Animals, Genetically Modified, Rats, Chemical and Drug Induced Liver Injury
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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