Int J Stem Cells.  2024 Aug;17(3):213-223. 10.15283/ijsc23176.

Navigating the Landscape of Intestinal Regeneration: A Spotlight on Quiescence Regulation and Fetal Reprogramming

Affiliations
  • 1Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Korea
  • 2Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Korea
  • 3Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Korea

Abstract

Tissue-specific adult stem cells are pivotal in maintaining tissue homeostasis, especially in the rapidly renewing intestinal epithelium. At the heart of this process are leucine-rich repeat-containing G protein-coupled receptor 5-expressing crypt base columnar cells (CBCs) that differentiate into various intestinal epithelial cells. However, while these CBCs are vital for tissue turnover, they are vulnerable to cytotoxic agents. Recent advances indicate that alternative stem cell sources drive the epithelial regeneration post-injury. Techniques like lineage tracing and single-cell RNA sequencing, combined with in vitro organoid systems, highlight the remarkable cellular adaptability of the intestinal epithelium during repair. These regenerative responses are mediated by the reactivation of conserved stem cells, predominantly quiescent stem cells and revival stem cells. With focus on these cells, this review unpacks underlying mechanisms governing intestinal regeneration and explores their potential clinical applications.

Keyword

Intestinal stem cells; Regeneration; Adult stem cells; Cellular reprogramming

Figure

  • Fig. 1 Various modulators involved in revival stem cell (RSC) induction. Several endogenous (niche-associated)- and exogenous (helminth infection, chemical stimuli) signals can activate yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) pathway, a crucial inducer for fetal reprogramming and RSC appearance in intestinal epithelium. Hpb: Heligmosomoides polygyrus bakeri, Th: helper T cell, Tc: cytotoxic T cell, IFN: interferon, TGF: transforming growth factor, PGE2: prostaglandin E2, RPPFs: rare pericryptal fibroblasts, IL: interleukin, VPA: valproic acid, EPZ: EPZ6438, RXR: retinoid X receptor, Clu: Clusterin.


Reference

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