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Cell Stem Cell. 2020 Jan 2;26(1):34-47.e3. doi: 10.1016/j.stem.2019.11.014. Epub 2019 Dec 19.

In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration.

Author information

1
Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA; Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo 102-0083, Japan.
2
Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
3
Gastroenterology and Hepatology, Stanford University, Stanford, CA 94305, USA.
4
Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: grompem@ohsu.edu.

Abstract

The identity of cellular populations that drive liver regeneration after injury is the subject of intense study, and the contributions of polyploid hepatocytes to organ regeneration and homeostasis have not been systematically assessed. Here, we developed a multicolor reporter allele system to genetically label and trace polyploid cells in situ. Multicolored polyploid hepatocytes undergo ploidy reduction and subsequent re-polyploidization after transplantation, providing direct evidence of the hepatocyte ploidy conveyor model. Marker segregation revealed that ploidy reduction rarely involves chromosome missegregation in vivo. We also traced polyploid hepatocytes in several different liver injury models and found robust proliferation in all settings. Importantly, ploidy reduction was seen in all injury models studied. We therefore conclude that polyploid hepatocytes have extensive regenerative capacity in situ and routinely undergo reductive mitoses during regenerative responses.

KEYWORDS:

hepatocyte; lineage tracing; ploidy conveyor; ploidy reduction; polyploidy

PMID:
31866222
DOI:
10.1016/j.stem.2019.11.014

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