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Murine breast cancers disorganize the liver transcriptome in zonated manners

Alexis Vandenbon, Rin Mizuno, Riyo Konishi, Masaya Onishi, Kyoko Masuda, Yuka Kobayashi, Hiroshi Kawamoto, Ayako Suzuki, Masahito Shimizu, Yasuhito Tanaka, Yutaka Suzuki, Shinpei Kawaoka
doi: https://doi.org/10.1101/2022.09.27.509354
Alexis Vandenbon
1Laboratory of Tissue Homeostasis, Institute for Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan
2Institute for Liberal Arts and Sciences, Kyoto University, Kyoto, 606-8507, Japan
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  • For correspondence: kawaokashinpei@gmail.com alexis.vandenbon@gmail.com ysuzuki@edu.k.u-tokyo.ac.jp
Rin Mizuno
3Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto, 606-8507, Japan
4Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
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Riyo Konishi
3Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto, 606-8507, Japan
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Masaya Onishi
5Graduate School of Frontier Science, The University of Tokyo, Chiba, 277-8562, Japan
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Kyoko Masuda
7Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan
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Yuka Kobayashi
7Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan
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Hiroshi Kawamoto
7Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan
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Ayako Suzuki
5Graduate School of Frontier Science, The University of Tokyo, Chiba, 277-8562, Japan
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Masahito Shimizu
8Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 501-1194, Japan
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Yasuhito Tanaka
9Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, 860-8556, Japan
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Yutaka Suzuki
5Graduate School of Frontier Science, The University of Tokyo, Chiba, 277-8562, Japan
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  • For correspondence: kawaokashinpei@gmail.com alexis.vandenbon@gmail.com ysuzuki@edu.k.u-tokyo.ac.jp
Shinpei Kawaoka
3Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto, 606-8507, Japan
6Department of Integrative Bioanalytics, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai 980-8575, Japan
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  • For correspondence: kawaokashinpei@gmail.com alexis.vandenbon@gmail.com ysuzuki@edu.k.u-tokyo.ac.jp
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Abstract

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 Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 28, 2022.
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Murine breast cancers disorganize the liver transcriptome in zonated manners
Alexis Vandenbon, Rin Mizuno, Riyo Konishi, Masaya Onishi, Kyoko Masuda, Yuka Kobayashi, Hiroshi Kawamoto, Ayako Suzuki, Masahito Shimizu, Yasuhito Tanaka, Yutaka Suzuki, Shinpei Kawaoka
bioRxiv 2022.09.27.509354; doi: https://doi.org/10.1101/2022.09.27.509354
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Murine breast cancers disorganize the liver transcriptome in zonated manners
Alexis Vandenbon, Rin Mizuno, Riyo Konishi, Masaya Onishi, Kyoko Masuda, Yuka Kobayashi, Hiroshi Kawamoto, Ayako Suzuki, Masahito Shimizu, Yasuhito Tanaka, Yutaka Suzuki, Shinpei Kawaoka
bioRxiv 2022.09.27.509354; doi: https://doi.org/10.1101/2022.09.27.509354

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