Dynamic zonation of liver polyploidy.
The liver is a polyploid organ, consisting of hepatocytes with one or two nuclei each containing 2, 4, 8 or more haploid chromosome sets. The dynamic changes in the spatial distributions of polyploid classes across the liver lobule, its repeating anatomical unit, have not been characterized. Identifying these spatial patterns is important for understanding liver homeostatic and regenerative turnover, as well as potential division of labor among ploidy classes. Here, we use single molecule-based tissue imaging to reconstruct the spatial zonation profiles of liver polyploid classes in mice of different ages. We find that liver polyploidy proceeds in spatial waves, advancing more rapidly in the mid-lobule zone compared to the periportal and perivenous zones. We also measure the spatial zonation profiles of S-phase entry at different ages and identify more rapid S-phase entry in the mid-lobule zone at older ages. Our findings reveal fundamental features of liver spatial heterogeneity and highlight their dynamic changes during development and aging.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Sivan
S
Tanami
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shani
S
Ben-Moshe
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Anat
A
Elkayam
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Avi
A
Mayo
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Keren
K
Bahar Halpern
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. shalev.itzkovitz@weizmann.ac.il.
Shalev
S
Itzkovitz
D000818:Animals; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000033:anatomy & histology*; D008297:Male; D008810:Mice, Inbred C57BL; D011123:Polyploidy; D016196:S Phase; D013997:Time Factors
Liver polyploidy; Liver zonation; Single molecule imaging; Stem cells; Systems biology