Wei ZX, Jiang SH, Qi XY, Cheng YM, Liu Q, Hou XY, He J. scRNA-seq of the intestine reveals the key role of mast cells in early gut dysfunction associated with acute pancreatitis. World J Gastroenterol 2025; 31(12): 103094 [DOI: 10.3748/wjg.v31.i12.103094]
Corresponding Author of This Article
Jun He, MD, Department of General Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road, Changsha 410011, Hunan Province, China. junjunhe@csu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Mar 28, 2025; 31(12): 103094 Published online Mar 28, 2025. doi: 10.3748/wjg.v31.i12.103094
scRNA-seq of the intestine reveals the key role of mast cells in early gut dysfunction associated with acute pancreatitis
Zu-Xing Wei, Shi-He Jiang, Xiao-Yan Qi, Yi-Miao Cheng, Qiong Liu, Xu-Yang Hou, Jun He
Zu-Xing Wei, Xiao-Yan Qi, Yi-Miao Cheng, Jun He, Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Shi-He Jiang, Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Qiong Liu, Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Xu-Yang Hou, Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Author contributions: He J designed the study; Wei ZX performed most of experiments, analyzed the data and wrote the manuscript; Jiang SH, Qi XY, Cheng YM, Liu Q, and Hou XY assisted with the experiments.
Supported by National Natural Science Foundation of China, No. 82300739; Hunan Provincial Natural Science Foundation, No. 2023JJ40821; and Changsha Natural Science Foundation, No. kq2208308.
Institutional animal care and use committee statement: All animal experiments employed appropriate measures to minimize pain or discomfort, and the experimental protocols were approved by the Animal Ethics Committee of Xiangya Second Hospital, Central South University (Approval No. 20200890).
Conflict-of-interest statement: The authors declare no conflict of interests.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Datasets are accessible directly via email communication with the corresponding author.
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: Jun He, MD, Department of General Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road, Changsha 410011, Hunan Province, China. junjunhe@csu.edu.cn
Received: November 10, 2024 Revised: January 9, 2025 Accepted: February 21, 2025 Published online: March 28, 2025 Processing time: 137 Days and 20 Hours
Abstract
BACKGROUND
Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis (AP). Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.
AIM
To explore the biological processes and mechanisms of intestinal injury associated with AP, and to find potential targets for early prevention or treatment of intestinal barrier injury.
METHODS
This study utilized single-cell RNA sequencing of the small intestine, alongside in vitro and in vivo experiments, to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.
RESULTS
Seventeen major cell types and 33232 cells were identified across all samples, including normal, AP1 (4x caerulein injections, animals sacrificed 2 h after the last injection), and AP2 (8x caerulein injections, animals sacrificed 4 h after the last injection). An average of 980 genes per cell was found in the normal intestine, compared to 927 in the AP1 intestine and 1382 in the AP2 intestine. B cells, dendritic cells, mast cells (MCs), and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine. Enterocytes, brush cells, enteroendocrine cells, and goblet cells maintained numbers similar to the normal intestine, while cytotoxic T cells and natural killer (NK) cells increased. Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities. Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities. Activated MCs, secreted chemokine (C-C motif) ligand 5 (CCL5), promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.
CONCLUSION
These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury, suggesting that CCL5 from MCs is a potential target for addressing dysfunction.
Core Tip: Our study provides a comprehensive picture of the transcriptome of small intestine cells during the early stage of acute pancreatitis, revealing a total of 33232 cells across all samples and 17 main clusters. Through our investigation, we established that mast cells (MCs) were promptly activated in the intestine, and we identified CCL5 derived from MCs as an indispensable factor contributing to the infiltration of inflammatory cells and the progression of gut barrier dysfunction.
