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Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing.

Authors :
Bai Y
Song Y
Li M
Ou J
Hu H
Xu N
Cao M
Wang S
Chen L
Cheng G
Li Z
Liu G
Wang J
Zhang W
Yang C
Source :
Journal of environmental sciences (China) [J Environ Sci (China)] 2024 Nov; Vol. 145, pp. 164-179. Date of Electronic Publication: 2023 Sep 09.
Publication Year :
2024

Abstract

The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern. Microcystin-leucine arginine (MC-LR) is a well-established toxin produced by cyanobacterial blooms, which is widely distributed in eutrophic waters. MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals. However, the underlying mechanisms of MC-LR-induced liver toxicity are unclear. Herein, we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice. We established the first single-cell atlas of mouse livers in response to MC-LR. Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treated with MC-LR are highly heterogeneous. Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3, which potentially contributed to hepatocyte apoptosis in response to MC-LR. Moreover, MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes. Furthermore, the MC-LR increased several subtypes of CD8 <superscript>+</superscript> T cells with highly expressed multiple cytokines and chemokines. Overall, apart from directly inducing hepatocytes apoptosis, MC-LR activated proinflammatory Kupffer cell and CD8 <superscript>+</superscript> T cells, and their interaction may constitute a hostile microenvironment that contributes to liver injury. Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.<br /> (Copyright © 2023. Published by Elsevier B.V.)

Details

Language :
English
ISSN :
1001-0742
Volume :
145
Database :
MEDLINE
Journal :
Journal of environmental sciences (China)
Publication Type :
Academic Journal
Accession number :
38844317
Full Text :
https://doi.org/10.1016/j.jes.2023.08.032