Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2023; 29(48): 6222-6234
Published online Dec 28, 2023. doi: 10.3748/wjg.v29.i48.6222
Single-cell analysis identifies phospholysine phosphohistidine inorganic pyrophosphate phosphatase as a target in ulcerative colitis
Yan-Fei Wang, Ruo-Yu He, Chan Xu, Xiao-Ling Li, Yan-Fei Cao
Yan-Fei Wang, Ruo-Yu He, Yan-Fei Cao, Department of Gastroenterology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, Xihu District, Hangzhou 310005, Zhejiang Province, China
Chan Xu, Clinical Laboratory, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, Xihu District, Hangzhou 310005, Zhejiang Province, China
Xiao-Ling Li, Elder Medicine Department, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, Xihu District, Hangzhou 310005, Zhejiang Province, China
Co-first authors: Yan-Fei Wang and Ruo-Yu He.
Author contributions: Cao YF designed and supervised the study, and drafted the manuscript; Wang YF and He RY took the responsibility for statistical analyses and the manuscript; Xu C and Li XL performed manuscript reviewing and editing; all authors have read and approved the article. The reasons for designating Wang YF and He RY as co-first authors are twofold. Wang YF is responsible for all bioinformatics computations and analyses, including handling data. He RY collects samples and conducts experiments. They contributed efforts of equal substance throughout the research process. Second, this study was a team effort, and the co-first authorship accurately reflects how responsibilities and work were shared during the study and paper completion. This helps with effective communication and managing post-submission tasks, ultimately improving the paper's quality and reliability. Summary, we believe that designating Wang YF and He RY as co-first authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.
Supported by Science and Technology Programme of Traditional Chinese Medicine in Zhejiang Province, No. 2023ZF114.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University (ZSLL-KY-2023-031-01).
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan-Fei Cao, PhD, Doctor, Department of Gastroenterology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, Hangzhou 310005, Zhejiang Province, China. zsyyxhky@126.com
Received: September 22, 2023
Peer-review started: September 22, 2023
First decision: November 20, 2023
Revised: November 27, 2023
Accepted: December 14, 2023
Article in press: December 14, 2023
Published online: December 28, 2023
Processing time: 95 Days and 16.4 Hours
Abstract
BACKGROUND

Ulcerative colitis (UC) is a chronic gastrointestinal disorder characterized by inflammation and ulceration, representing a significant predisposition to colorectal cancer. Recent advances in single-cell RNA sequencing (scRNA-seq) technology offer a promising avenue for dissecting the complex cellular inter-actions and molecular signatures driving UC pathology.

AIM

To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology.

METHODS

In this research, we integrated and analyzed the scRNA-seq data from UC patients. Moreover, we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples.

RESULTS

In this study, we identified the sustained upregulation of inflammatory response pathways during UC progression, characterized the features of damaged endo-thelial cells in colitis. Furthermore, we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has a negative correlation with signal transducer and activator of transcription 3. Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC. This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation.

CONCLUSION

The findings suggest that LHPP may serve as a potential therapeutic target for UC, emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.

Keywords: Ulcerative colitis; Single-cell RNA sequencing; Phospholysine phosphohistidine inorganic pyrophosphate phosphatase

Core Tip: Ulcerative colitis (UC), a chronic inflammatory bowel disease linked to colorectal cancer, was investigated using single-cell RNA sequencing technology. The study unveiled sustained upregulation of inflammatory response pathways and characterized damaged endothelial cells during UC progression. Notably, the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) exhibited a negative correlation with signal transducer and activator of transcription 3. LHPP's significant downregulation in UC patient tissues and plasma suggests its potential as a therapeutic target. The findings highlight LHPP as a key target in UC and emphasize its role in inflammation regulation, offering insights for potential therapeutic interventions.