Diploid hepatocytes drive physiological liver renewal in adult humans
Open accessAbstract
Physiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon ( 14 C) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age <3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show more than 7-fold higher annual birth rates than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between diploid and polyploid hepatocytes are limited under homeostatic conditions. With these findings, we present an integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.
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The liver requires much lower proliferation rates than high-turnover organs that are maintained by constantly cycling tissue stem cell compartments, due to extended hepatocyte lifespan.
“Given the extended hepatocyte lifespan (200–300 days in rodents10 and 3 years in human11) the liver requires much lower proliferation rates than high-turnover organs that are maintained by constantly cycling tissue stem cell compartments.”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [11]
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Flagged first, then by citations
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Cited by
Sorted by citations
Distinct hepatocyte identities in liver homeostasis and regeneration
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- Authors
- Heinke, P., Rost, F., Rode, J., Trus, P., Simonova, I., Lázár, E., Feddema, J., Welsch, T., Alkass, K., Salehpour, M., Zimmermann, A., Seehofer, D., Possnert, G., Damm, G., Druid, H., Brusch, L., & Bergmann, O.
- Affiliations
- Center for Regenerative Therapies Dresden (DE)
- Max Planck Institute for the Physics of Complex Systems (DE)
- Center for Information Services and High Performance Computing (DE)
- Karolinska Institutet (SE)
- University Hospital Carl Gustav Carus (DE)
- Uppsala University (SE)
- Leipzig University (DE)
- Corresponding author
- Bergmann, Olaf
- ORCID
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 13
- Issue
- 6
- Pages
- 499-507.e12
- ISSN
- 2405-4712 (ISSN-L)
- OpenAlex
- W4282941596
- Cited by
- 73
- References
- 15
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 18 · 2023: 17 · 2022: 4 · 2021: 1
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Funders
- Fondation Leducq
- Bundesministerium für Bildung und Forschung (031L0033, 031L0258A)
- Åke Wiberg Stiftelse
- Karolinska Institutet
- Vetenskapsrådet
- Zentrum für Regenerative Therapien Dresden
- Ragnar Söderbergs stiftelse
- Zentrum für Informationsdienste und Hochleistungsrechnen, Technische Universität Dresden
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- hepatocyte turnover, cell ploidy, liver homeostasis
- MeSH terms
- Adult, Child, Preschool, Diploidy, Humans, Liver, Polyploidy, Retrospective Studies, Hepatocytes
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