Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair
Abstract
Zoning in on liver growth: For organ homeostasis or regrowth after injury or disease, one or more stem cell populations is needed to rebuild lost tissue. There is considerable debate about the source of new cells in the liver. Two groups now identify the source of new hepatocytes (see the Perspective by Andersson). Although the liver may seem to lack major variation across its structure, its lobule is organized into concentric zones where hepatocytes express different metabolic enzymes. Wei et al. sought to systematically define the source of new liver cells by comparing 14 fate-mapping mice that label different liver cell types. They found that different regions of the liver lobule exhibit differences in hepatocyte turnover, with zone 2 representing a primary source of new hepatocytes during homeostasis and regeneration. Similarly, He et al. designed a genetic approach to record cell proliferation in vivo with high spatial and temporal resolution to enable continuous recording of proliferative events of any specific cell type at the whole-cell population level. Using this method, they identified zone 2 as having the highest proliferative activity and contributing the most to liver regrowth. These findings have implications for the cellular basis of chronic disease pathogenesis, cancer development, and regenerative medicine strategies. Science , this issue p. eabb1625 , p. eabc4346 ; see also p. 887
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recent studies have demonstrated that hepatocytes are primarily maintained by the proliferation of pre-existing hepatocytes during liver homeostasis and regeneration.
“recent studies have demonstrated that hepatocytes are primarily maintained by the proliferation of pre-existing hepatocytes during liver homeostasis and regeneration14–19”
From Multimodal decoding of human liver regeneration (2024) · cites this paper as [17]
During homeostasis, zone 2 hepatocytes rather than a defined subpopulation seem to have increased proliferative potential.
“During homeostasis, zone 2 hepatocytes rather than a defined subpopulation seem to have increased proliferative potential.”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [75]
Hepatocytes do not proliferate equally over time, as results obtained via three independent experimental approaches have led to the same conclusion, namely that zone 2 hepatocytes proliferate more than hepatocytes from the other zones.
“Nevertheless, hepatocytes do not proliferate equally over time, as results obtained via three independent experimental approaches have led to the same conclusion, namely that zone 2 hepatocytes proliferate more than hepatocytes from the other zones.75,86,88”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [75]
In the absence of injury, hepatocytes in zone 2 have a proliferation rate of 0.042 per week.
“In the absence of injury, hepatocytes in zone 2 have a proliferation rate of 0.042 per week.75”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [75]
There is more proliferation in zone 2 compared to zones 1 and 3 during homeostasis.
“A novel method using a “ProTracer” mouse transgenic line that records cell division demonstrated that there is more proliferation in zone 2 compared to zones 1 and 3 during homeostasis.75”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [75]
The citation lists haven’t been fetched yet
References 65 · Cited by 261
- Authors
- He, L., Pu, W., Liu, X., Zhang, Z., Han, M., Li, Y., Huang, X., Han, X., Li, Y., Liu, K., Shi, M., Lai, L., Sun, R., Wang, Q.-D., Ji, Y., Tchorz, J. S., & Zhou, B.
- Affiliations
- Chinese Academy of Sciences (CN)
- Shanghai Model Organisms (China) (CN)
- AstraZeneca (Sweden) (SE)
- Nanjing Medical University (CN)
- Novartis (Switzerland) (CH)
- Corresponding author
- He, Lingjuan
- Pu, Wenjuan
- Liu, Xiuxiu
- Zhou, Bin
- ORCID
- Venue
- Science
- Published
- 2021-02-26
- Volume
- 371
- Issue
- 6532
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3130345333
- Cited by
- 261
- References
- 65
- Citations by year
- 2026: 37 · 2025: 62 · 2024: 37 · 2023: 50 · 2022: 42 · 2021: 33
- FWCI
- 22.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- China Postdoctoral Science Foundation
- National Key Research and Development Program of China Stem Cell and Translational Research (2019YFA0110403, 2018YFA0107900, 2019YFA0802000, 2018YFA0108100, 2017YFC1001303)
- National Science Foundation of China (31730112, 31625019, 91849202, 81761138040, 81872241, 31922032)
- The Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000, XDA16010507)
- Shanghai Rising Star Project
- Innovative research team of high-level local universities in Shanghai, Shanghai Science and Technology Commission (19ZR1479800, 17ZR1449600)
- Royal Society-Newton Advanced Fellowship
- Youth Innovation Promotion Association of CAS, Key Project of Frontier Sciences of CAS (QYZDB-SSW-SMC003)
- the Program for Guangdong Introduction Innovative and Entrepreneurial Teams (2017ZT07S347)
- China Postdoctoral Innovative Talent Support Program
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- hepatocyte proliferation, liver regeneration, liver homeostasis, cell fate mapping, liver stem cells, hepatocyte turnover
- MeSH terms
- Animals, Hepatectomy, Homeostasis, Liver, Liver Regeneration, Ki-67 Antigen, Hepatocytes, Cell Proliferation, Mice, Chemical and Drug Induced Liver Injury, Cyclin A2
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 ›
Are you an author, or do you see a problem with this page? Request a review
