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World J Stem Cells. May 26, 2023; 15(5): 354-368
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.354
Modulation of stem cell fate in intestinal homeostasis, injury and repair
Zhe Wang, Yan-Ji Qu, Min Cui
Zhe Wang, Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Yan-Ji Qu, Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Min Cui, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Wang Z wrote the manuscript; Qu YJ collected the data; Cui M revised and approved the manuscript; All authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82202766; the Natural Science Foundation of Hubei Province of China, No. 2022CFB686; the Science Foundation of Union Hospital, No. 2021xhyn102; and the Scientific Research Training Program for Young Talents in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Min Cui, MD, PhD, Associate Chief Physician, Associate Professor, Doctor, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China. cm95588@hust.edu.cn
Received: January 14, 2023
Peer-review started: January 14, 2023
First decision: March 21, 2023
Revised: March 31, 2023
Accepted: April 24, 2023
Article in press: April 24, 2023
Published online: May 26, 2023
Abstract

The mammalian intestinal epithelium constitutes the largest barrier against the external environment and makes flexible responses to various types of stimuli. Epithelial cells are fast-renewed to counteract constant damage and disrupted barrier function to maintain their integrity. The homeostatic repair and regeneration of the intestinal epithelium are governed by the Lgr5+ intestinal stem cells (ISCs) located at the base of crypts, which fuel rapid renewal and give rise to the different epithelial cell types. Protracted biological and physicochemical stress may challenge epithelial integrity and the function of ISCs. The field of ISCs is thus of interest for complete mucosal healing, given its relevance to diseases of intestinal injury and inflammation such as inflammatory bowel diseases. Here, we review the current understanding of the signals and mechanisms that control homeostasis and regeneration of the intestinal epithelium. We focus on recent insights into the intrinsic and extrinsic elements involved in the process of intestinal homeostasis, injury, and repair, which fine-tune the balance between self-renewal and cell fate specification in ISCs. Deciphering the regulatory machinery that modulates stem cell fate would aid in the development of novel therapeutics that facilitate mucosal healing and restore epithelial barrier function.

Keywords: Intestinal stem cell, Epithelial repair, Homeostasis, Regeneration, Self-renewal, Apoptosis

Core Tip: The homeostatic repair and regeneration of the intestinal epithelium upon injury are governed by the Lgr5+ intestinal stem cells (ISCs) located at the base of crypts, which fuel rapid renewal and give rise to different epithelial cell types. We review the current understanding of the intrinsic niche signaling and extrinsic stimulating factors that control homeostasis and regeneration of the ISCs. Deciphering the regulatory machinery that modulates stem cell fate, and formulating strategies for better repair and regeneration would aid in the development of novel therapeutics that facilitate mucosal healing and restore epithelial barrier function.