Identification of glutathione metabolism-related biomarkers in non-alcoholic fatty liver disease based on single-cell and bulk RNA sequencing.
- 1Clinical Medical College of Qinghai University, Qinghai, China.
- 2Department of Hepatology II, Fourth People's Hospital of Qinghai Province, Qinghai, China.
- 3Department of Public Health and Hospital Infection Management, Qinghai University Affiliated Hospital, Qinghai, China. [email protected].
Abstract
Background
Glutathione (GSH) metabolism plays a crucial role in the development and progression of non-alcoholic fatty liver disease (NAFLD), yet its molecular mechanism remains unclear.Methods
Bulk transcriptome and single-cell data from the Gene Expression Omnibus (GEO) database were analyzed using single-cell RNA sequencing (scRNA-seq) and five algorithms for Glutathione metabolism-related genes (GMRGs) scores to identify key cell types and biomarkers. Core candidate biomarker was validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting in palmitic acid (PA)-induced HepG2 cells.Results
Cholangiocytes showed the highest GMRG-related transcriptional activity among the annotated cell populations. Through screening, 4 potential biomarkers (CSTA, DDAH2, OAZ2, TYMP) were found, with DDAH2 as the core due to its high expression and strong correlation with GMRGs. Enrichment analysis suggested that DDAH2 expression was associated with energy metabolism and protein homeostasis pathways. DDAH2-high cholangiocytes showed stronger computationally inferred interactions with B cells and endothelial cells, mainly involving the "MIF-(CD74 + CXCR4)" and "APP-CD74" pathways, and were enriched in early pseudotime states. In vitro, DDAH2 expression was significantly up-regulated in NAFLD, providing preliminary support for the expression trend.Conclusion
This study identified cholangiocytes as the annotated cell population with the strongest GSH metabolism-related transcriptional signature in the analyzed NAFLD scRNA-seq dataset and highlighted four related biomarkers, with DDAH2 prioritized as the core candidate biomarker.
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BibTeX
@article{zhao2026identification,
title = {{Identification of glutathione metabolism-related biomarkers in non-alcoholic fatty liver disease based on single-cell and bulk RNA sequencing.}},
author = {Yinan Zhao and Guoying Yu and Lu Zhao},
journal = {BMC medical genomics},
year = {2026},
month = jul,
doi = {10.1186/s12920-026-02444-0},
url = {https://europepmc.org/article/MED/42958345},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Identification of glutathione metabolism-related biomarkers in non-alcoholic fatty liver disease based on single-cell and bulk RNA sequencing.
AU - Yinan Zhao
AU - Guoying Yu
AU - Lu Zhao
PY - 2026
DA - 2026/07/29
JO - BMC medical genomics
DO - 10.1186/s12920-026-02444-0
UR - https://europepmc.org/article/MED/42958345
AB - Background Glutathione (GSH) metabolism plays a crucial role in the development and progression of non-alcoholic fatty liver disease (NAFLD), yet its molecular mechanism remains unclear.Methods Bulk transcriptome and single-cell data from the Gene Expression Omnibus (GEO) database were analyzed using single-cell RNA sequencing (scRNA-seq) and five algorithms for Glutathione metabolism-related genes (GMRGs) scores to identify key cell types and biomarkers. Core candidate biomarker was validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting in palmitic acid (PA)-induced HepG2 cells.Results Cholangiocytes showed the highest GMRG-related transcriptional activity among the annotated cell populations. Through screening, 4 potential biomarkers (CSTA, DDAH2, OAZ2, TYMP) were found, with DDAH2 as the core due to its high expression and strong correlation with GMRGs. Enrichment analysis suggested that DDAH2 expression was associated with energy metabolism and protein homeostasis pathways. DDAH2-high cholangiocytes showed stronger computationally inferred interactions with B cells and endothelial cells, mainly involving the "MIF-(CD74 + CXCR4)" and "APP-CD74" pathways, and were enriched in early pseudotime states. In vitro, DDAH2 expression was significantly up-regulated in NAFLD, providing preliminary support for the expression trend.Conclusion This study identified cholangiocytes as the annotated cell population with the strongest GSH metabolism-related transcriptional signature in the analyzed NAFLD scRNA-seq dataset and highlighted four related biomarkers, with DDAH2 prioritized as the core candidate biomarker.
SN - 1755-8794
ER -