ArticleThe Journal of cell biology2024
Binucleated human hepatocytes arise through late cytokinetic regression during endomitosis M phase.
Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- The immediate cellular response to whole-genome doubling is conserved across polyploid contexts.bioRxiv : the preprint server for biology · 2026Article
- Morphological and Immunohistochemical Characteristics of Liver Inflammation in Patients with a History of COVID-19.Viruses · 2026Article
- Optimized Protocol for Primary Rat Hepatocyte Isolation and a Model for Investigating Experimental Steatosis.Methods and protocols · 2025Article
- Metronidazole induces genotoxicity, hepato- and nephrotoxicity by triggering DNA fragmentation in Swiss albino mice (Balb/c).Scientific reports · 2025Article
- Ascending E2F7a/b ratio facilitates KLF13 transcription in hepatocellular carcinoma and correlates with the abundance of binuclear hepatocytes (ABH) modulation for short-term recurrence.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Temporal myc dynamics permit mitotic bypass, promoting polyploid phenotypes.Cancer letters · 2025Review
- Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes.Journal of Zhejiang University. Science. BReview
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Authors and funding
5 authors.
Funding
Abstract
Binucleated polyploid cells are common in many animal tissues, where they arise by endomitosis, a non-canonical cell cycle in which cells enter M phase but do not undergo cytokinesis. Different steps of cytokinesis have been shown to be inhibited during endomitosis M phase in rodents, but it is currently unknown how human cells undergo endomitosis. In this study, we use fetal-derived human hepatocyte organoids (Hep-Orgs) to investigate how human hepatocytes initiate and execute endomitosis. We find that cells in endomitosis M phase have normal mitotic timings, but lose membrane anchorage to the midbody during cytokinesis, which is associated with the loss of four cortical anchoring proteins, RacGAP1, Anillin, SEPT9, and citron kinase (CIT-K). Moreover, reduction of WNT activity increases the percentage of binucleated cells in Hep-Orgs, an effect that is dependent on the atypical E2F proteins, E2F7 and E2F8. Together, we have elucidated how hepatocytes undergo endomitosis in human Hep-Orgs, providing new insights into the mechanisms of endomitosis in mammals.
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