TY - JOUR
T1 - Single-cell transcriptomic insights into endosulfan-induced liver injury: key pathways and inflammatory responses
AU - Huang, Pan
AU - Bai, Yunmeng
AU - Zhou, Chaohua
AU - Zhong, Xiaoru
AU - Iyaswamy, Ashok
AU - Chen, Peng
AU - Wei, Xu
AU - Zhang, Wei
AU - Yang, Chuanbin
AU - Wang, Jigang
N1 - The work was supported by grants from the National Key Research and Development Program of China (No. 2022YFC2303603 and 2020YFA0908004), National Natural Science Foundation of China (No.U24A20798 and 82374063), the Shenzhen Science and Technology Program (No. JCYJ20220818102613029), China Postdoctoral Science Foundation (No. 2024M752143), the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (No. CI2021B014); the Shenzhen Medical Research Funds (No. B2302051).
Publisher Copyright:
© 2025 The Third Affiliated Hospital of Sun Yat-sen University.
PY - 2025/6
Y1 - 2025/6
N2 - Background and aims Environmental pollutants, particularly organochlorine insecticides like Endosulfan (ENDO), are increasingly linked to liver toxicity and related diseases. Despite its widespread historical use, the mechanisms underlying ENDO-induced liver damage remain poorly understood. This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity. Methods C57BL/6 mice were exposed to ENDO for 2 weeks. Single-cell RNA sequencing (scRNA-seq) was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level. Differentially expressed genes (DEGs) across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO. Transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure. Results ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells with and lymphocytes, triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes. Additionally, ENDO exposure led to the recruitment and activation of myeloid cells, contributing to the inflammatory milieu. Increased in intercellular communication and changes to the hepatic microenvironment, especially the interaction of activated hepatic stellate cell to CD8+ T cells were observed, further implicating these processes in ENDO-induced liver damage. Conclusions This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO. Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution. These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.
AB - Background and aims Environmental pollutants, particularly organochlorine insecticides like Endosulfan (ENDO), are increasingly linked to liver toxicity and related diseases. Despite its widespread historical use, the mechanisms underlying ENDO-induced liver damage remain poorly understood. This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity. Methods C57BL/6 mice were exposed to ENDO for 2 weeks. Single-cell RNA sequencing (scRNA-seq) was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level. Differentially expressed genes (DEGs) across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO. Transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure. Results ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells with and lymphocytes, triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes. Additionally, ENDO exposure led to the recruitment and activation of myeloid cells, contributing to the inflammatory milieu. Increased in intercellular communication and changes to the hepatic microenvironment, especially the interaction of activated hepatic stellate cell to CD8+ T cells were observed, further implicating these processes in ENDO-induced liver damage. Conclusions This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO. Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution. These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.
KW - Endosulfan (ENDO)
KW - Hepatic microenvironment
KW - Inflammatory responses
KW - Intercellular communication
KW - Liver injury / hepatotoxicity
KW - Single-cell RNA sequencing (scRNA-seq)
UR - http://www.scopus.com/inward/record.url?scp=105008129794&partnerID=8YFLogxK
U2 - 10.1016/j.livres.2025.05.002
DO - 10.1016/j.livres.2025.05.002
M3 - Journal article
SN - 2542-5684
VL - 9
SP - 144
EP - 156
JO - Liver Research
JF - Liver Research
IS - 2
ER -
