Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice

Wu, Jiangpeng1,2; Sun, Xiuping1,2; Wu, Chunyi1,2; Hong, Xiaoping3; Xie, Lulin1,2; Shi, Zixu1,2; Zhao, Liang7,8,9; Du, Qingfeng5; Xiao, Wei4,6; Sun, Jichao1,2; Wang, Jigang1,2,5,6,10,11

2023-02-04

10.1186/s11658-023-00426-z

CELLULAR & MOLECULAR BIOLOGY LETTERS   Impact Factor & Quartile

1425-8153

1689-1392

Background: Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown.Methods: Using single-cell RNA sequencing (scRNA-seq), immunofluorescent staining, and in vivo animal studies, we analyzed the liver tissues from untreated and GLY-treated mice.Results: We generated the first scRNA-seq atlas of GLY-exposed mouse liver. GLY induced varied cell composition, shared or cell-type-specific transcriptional alterations, and dysregulated cell-cell communication and thus exerted hepatotoxicity effects. The oxidative stress and inflammatory response were commonly upregulated in several cell types. We also observed activation and upregulated phagocytosis in macrophages, as well as proliferation and extracellular matrix overproduction in hepatic stellate cells.Conclusions:Our study provides a comprehensive single-cell transcriptional picture of the toxic effect of GLY in the liver, which offers novel insights into the molecular mechanisms of the GLY-associated hepatotoxicity.

Glyphosate Hepatotoxicity scRNA-seq

SCI

English

First ; Corresponding

National Natural Science Foundation of China["82071193","32000673","82141001","82274182","82074098","82173914"] ; Science and Technology Innovation Committee of Shenzhen[RCYX20210706092040044] ; China Postdoctoral Science Foundation[K122292027] ; National Key Research and Development Program of China["2020YFA0908000","2022YFC2303600"] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; Science and Technology Foundation of Shenzhen["JCYJ20210324115800001","JCYJ20220818102613029"] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173612034] ; Shenzhen key Laboratory of Kidney Diseases[ZDSYS201504301616234] ; Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties[SZGSP001]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000926459300001

BMC

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Clin Med Coll 2,Dept Nephrol,Shenzhen Key Lab Kidn, Shenzhen 518020, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Clin Res Ctr Geriatr, Affiliated Hosp 1,Shenzhen Peoples Hosp,Clin Med C, Shenzhen 518020, Peoples R China
3.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Dept Rheumatol & Immunol,Shenzhen Peoples Hosp,Cl, Shenzhen 518020, Peoples R China
4.Guangdong Pharmaceut Univ, Key Lab Glucolipid Metab Disorder, Minist Educ, Guangzhou 510006, Peoples R China
5.Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Peoples R China
6.Southern Med Univ, Dongguan Maternal & Child Hlth Care Hosp, Postdoctoral Innovat Practice Base, Dongguan 523125, Guangdong, Peoples R China
7.Southern Med Univ, Shunde Hosp, Peoples Hosp Shunde 1, Dept Pathol, Foshan 528300, Peoples R China
8.Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou 510515, Peoples R China
9.Southern Med Univ, Sch Basic Med Sci, Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou 510515, Peoples R China
10.China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
11.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

Wu, Jiangpeng,Sun, Xiuping,Wu, Chunyi,et al. Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice[J]. CELLULAR & MOLECULAR BIOLOGY LETTERS,2023,28(1).

Wu, Jiangpeng.,Sun, Xiuping.,Wu, Chunyi.,Hong, Xiaoping.,Xie, Lulin.,...&Wang, Jigang.(2023).Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.CELLULAR & MOLECULAR BIOLOGY LETTERS,28(1).

Wu, Jiangpeng,et al."Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice".CELLULAR & MOLECULAR BIOLOGY LETTERS 28.1(2023).