RT Journal Article
SR Electronic
T1 Murine breast cancers disorganize the liver transcriptome in zonated manners
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.27.509354
DO 10.1101/2022.09.27.509354
A1 Vandenbon, Alexis
A1 Mizuno, Rin
A1 Konishi, Riyo
A1 Onishi, Masaya
A1 Masuda, Kyoko
A1 Kobayashi, Yuka
A1 Kawamoto, Hiroshi
A1 Suzuki, Ayako
A1 Shimizu, Masahito
A1 Tanaka, Yasuhito
A1 Suzuki, Yutaka
A1 Kawaoka, Shinpei
YR 2022
UL http://biorxiv.org/content/early/2022/09/28/2022.09.27.509354.abstract
AB The spatially organized gene expression program within the liver specifies hepatocyte functions according to their relative distances to the bloodstream (i.e., zonation), contributing to liver homeostasis. Despite the knowledge that solid cancers remotely disrupt liver homeostasis, it remains unexplored whether solid cancers affect liver zonation. Here, using spatial transcriptomics, we thoroughly investigate the abundance and zonation of hepatic genes in cancer-bearing mice. We find that breast cancers affect liver zonation in various distinct manners depending on biological pathways. Aspartate metabolism and triglyceride catabolic processes retain relatively intact zonation patterns, but the zonation of xenobiotic catabolic process genes exhibits a strong disruption. The acute phase response is induced in zonated manners. Furthermore, we demonstrate that breast cancers activate innate immune cells in particular neutrophils in distinct zonated manners, rather than in a uniform fashion within the liver. Collectively, breast cancers disorganize hepatic transcriptomes in zonated manners, thereby disrupting zonated functions of the liver.Competing Interest StatementThe authors have declared no competing interest.