TY - JOUR
T1 - Murine breast cancers disorganize the liver transcriptome in a zonated manner
AU - Vandenbon, Alexis
AU - Mizuno, Rin
AU - Konishi, Riyo
AU - Onishi, Masaya
AU - Masuda, Kyoko
AU - Kobayashi, Yuka
AU - Kawamoto, Hiroshi
AU - Suzuki, Ayako
AU - He, Chenfeng
AU - Nakamura, Yuki
AU - Kawaguchi, Kosuke
AU - Toi, Masakazu
AU - Shimizu, Masahito
AU - Tanaka, Yasuhito
AU - Suzuki, Yutaka
AU - Kawaoka, Shinpei
N1 - Funding Information:
We thank Dr. Diego Diez (Osaka University) and Prof. Kosuke Yusa (Kyoto University) for their helpful discussions and advice. This work was supported by JSPS KAKENHI (16H06279, 18K15409, 18H04810, 20H03451, 20H04842, and 22H04925; S.K., and 20K06609; A.V.), JST FOREST (JPMJFR2062; S.K.), JST Moonshot (JPMJMS2011-61; S.K.), Caravel, Co., Ltd (S.K.), Ono Medical Research Foundation (S.K), Takeda Science Foundation, The Uehara memorial foundation (S.K.), Chubei Ito foundation (S.K.) and Japan Foundation for Applied Enzymology (S.K). We thank Yuri Kawaoka for drawing the cartoons in Fig. .
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
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.
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U2 - 10.1038/s42003-023-04479-w
DO - 10.1038/s42003-023-04479-w
M3 - Article
C2 - 36694005
AN - SCOPUS:85146758258
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 97
ER -
