Research Alert

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.

Key Words: 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.



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