Binucleated human hepatocytes arise through late cytokinetic regression during endomitosis M phase.
J Cell Biol
; 223(8)2024 Aug 05.
Article
in En
| MEDLINE
| ID: mdl-38727809
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organoids
/
Hepatocytes
/
Cytokinesis
/
Mitosis
Limits:
Humans
Language:
En
Journal:
J Cell Biol
Year:
2024
Document type:
Article
Affiliation country: