Intestinal Regeneration: Regulation by the Microenvironment

• Published in: Developmental cell Vol. 54; no. 4; pp. 435 - 446
• Main Authors: Hageman, Joris H., Heinz, Maria C., Kretzschmar, Kai, van der Vaart, Jelte, Clevers, Hans, Snippert, Hugo J.G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.08.2020
• Subjects: Cell Cycle Proteins - genetics; Cell Dedifferentiation - genetics; Cell Lineage - genetics; Cellular Microenvironment - genetics; cellular plasticity; colon; dedifferentiation; epithelial damage; Humans; immune cells; intestine; Intestines - cytology; Intestines - growth & development; Lgr5; mesenchymal cells; niche; Receptors, Notch - genetics; Regeneration - genetics; stem cell; Stem Cells - cytology; Transcription Factors - genetics; Wnt Signaling Pathway - genetics; intestine; stem cell; epithelial damage; cellular plasticity; colon; dedifferentiation; immune cells; Lgr5; niche; mesenchymal cells
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2020.07.009

Damage to the intestinal stem cell niche can result from mechanical stress, infections, chronic inflammation or cytotoxic therapies. Progenitor cells can compensate for insults to the stem cell population through dedifferentiation. The microenvironment modulates this regenerative response by influencing the activity of signaling pathways, including Wnt, Notch, and YAP/TAZ. For instance, mesenchymal cells and immune cells become more abundant after damage and secrete signaling molecules that promote the regenerative process. Furthermore, regeneration is influenced by the nutritional state, microbiome, and extracellular matrix. Here, we review how all these components cooperate to restore epithelial homeostasis in the intestine after injury. Hageman et al. present a review discussing the role of the microenvironment in regulating regeneration in the intestine. The microenvironment responds to damage from mechanical stress, infections, chronic inflammation, or cytotoxic therapies by affecting the activity of signaling pathways, including Wnt, Notch, and YAP/TAZ.