Hypertrophy and Unconventional Cell Division of Hepatocytes Underlie Liver Regeneration
Open accessAbstract
Background The size of organs and tissues is basically determined by the number and size of their cells. However, little attention has been paid to this fundamental concept. The liver has a remarkable ability to regenerate after surgical resection (partial hepatectomy [PHx]), and hepatocytes account for about 80% of liver weight, so we investigate how the number and size of hepatocytes contribute to liver regeneration in mice. It has been generally accepted that hepatocytes undergo one or two rounds of cell division after 70% PHx. However, ploidy of hepatocytes is known to increase during regeneration, suggesting an unconventional cell cycle. We therefore examine cell cycle of hepatocytes in detail. Results By developing a method for genetic fate mapping and a high-throughput imaging system of individual hepatocytes, we show that cellular hypertrophy makes the first contribution to liver regeneration; i.e., regeneration after 30% PHx is achieved solely by hypertrophy without cell division, and hypertrophy precedes proliferation after 70% PHx. Proliferation and hypertrophy almost equally contribute to regeneration after 70% PHx. Furthermore, although most hepatocytes enter cell cycle after 70% PHx, not all hepatocytes undergo cell division. In addition, binuclear hepatocytes undergo reductive divisions to generate two mononuclear daughter hepatocytes in some cases. Conclusions Our findings demonstrate the importance of hypertrophy and the unconventional cell division cycle of…
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Minor resections tend to induce hypertrophic regeneration, characterized by enlargement of existing hepatocytes.
“Minor resections tend to induce hypertrophic regeneration, characterized by enlargement of existing hepatocytes.”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [5]
When no more than 30% of the liver mass is resected, the intrahepatic portal pool is not reduced enough to initiate mitotic activity, but it is sufficient to induce hypertrophic regeneration.
“Conversely, when no more than 30% of the liver mass is resected, the intrahepatic portal pool is not reduced to an extent that would initiate mitotic activity. However, it is sufficient to induce hypertrophic regeneration[5].”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [5]
More recent evidence highlights hypertrophy as a critical compensatory mechanism, particularly in cases where proliferation is delayed or suppressed.
“more recent evidence highlights hypertrophy as a critical, compensatory mechanism, particularly in cases where proliferation is delayed or suppressed[5,6].”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [5]
Major resections lead to hyperplastic regeneration, driven by both hypertrophy and cell proliferation.
“Major resections, by contrast, lead to hyperplastic regeneration, driven by both hypertrophy and cell proliferation[5,7].”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [5]
Hypertrophy predominates after minor resections, while proliferation is dominant in larger resections.
“noting that hypertrophy predominates after minor resections, while proliferation is dominant in larger resections.”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [5]
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- Authors
- Miyaoka, Y., Ebato, K., Kato, H., Arakawa, S., Shimizu, S., & Miyajima, A.
- Affiliations
- The University of Tokyo (JP)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Miyajima, Atsushi
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 22
- Issue
- 13
- Pages
- 1166-1175
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W1972126834
- Cited by
- 461
- References
- 3
- Citations by year
- 2026: 15 · 2025: 32 · 2024: 39 · 2023: 51 · 2022: 47 · 2021: 43 · 2020: 39 · 2019: 31 · 2018: 51 · 2017: 26 · 2016: 27 · 2015: 19 · 2014: 24 · 2013: 14 · 2012: 3
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23657084, 22229002)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- liver regeneration, hepatocyte hypertrophy, hepatocyte proliferation, partial hepatectomy, cell cycle, polyploidy, binuclear hepatocytes, genetic fate mapping, hepatocyte size
- MeSH terms
- Animals, Cell Division, Cell Nucleus, Hepatectomy, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Mitosis, Organ Size, Image Cytometry, Hepatocytes, Cell Enlargement, Cell Proliferation, Mice, Single-Cell Analysis
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