Int J Stem Cells.  2024 Feb;17(1):51-58. 10.15283/ijsc23172.

Host-Microbe Interactions Regulate Intestinal Stem Cells and Tissue Turnover in Drosophila

Affiliations
  • 1National Creative Research Initiative Center for Hologenomics and School of Biological Sciences, Seoul National University, Seoul, Korea
  • 2The Research Institute of Basic Sciences, Seoul National University, Seoul, Korea

Abstract

With the activity of intestinal stem cells and continuous turnover, the gut epithelium is one of the most dynamic tissues in animals. Due to its simple yet conserved tissue structure and enteric cell composition as well as advanced genetic and histologic techniques, Drosophila serves as a valuable model system for investigating the regulation of intestinal stem cells. The Drosophila gut epithelium is in constant contact with indigenous microbiota and encounters externally introduced “non-self” substances, including foodborne pathogens. Therefore, in addition to its role in digestion and nutrient absorption, another essential function of the gut epithelium is to control the expansion of microbes while maintaining its structural integrity, necessitating a tissue turnover process involving intestinal stem cell activity. As a result, the microbiome and pathogens serve as important factors in regulating intestinal tissue turnover. In this manuscript, I discuss crucial discoveries revealing the interaction between gut microbes and the host’s innate immune system, closely associated with the regulation of intestinal stem cell proliferation and differentiation, ultimately contributing to epithelial homeostasis.

Keyword

Drosophila; Intestines; Stem cells; Epithelium; Microbiota,; Reactive oxygen species

Figure

  • Fig. 1 Proliferation and differentiation of intestinal stem cell (ISC) in Drosophila. The division of an ISC produces either a new ISC for self-renewal, an enteroendocrine mother cell (EMC) capable of producing enteroendocrine cell (EEC) through cell division or an enteroblast (EB) for further differentiation into an enterocyte (EC).

  • Fig. 2 Host-microbe interactions shape intestinal stem cell (ISC) proliferation and tissue turnover. Peptidoglycan (PG) from gut microbe activates the IMD pathway in enterocytes, leading to the production of antimicrobial peptide (AMP), which is a bactericidal effector molecule. Pathogens and pathobionts produce uracil, which activates the dual oxidase (DUOX) pathway and triggers the oxidative burst. Enterocytes damaged by reactive oxygen species (ROS) from the host and virulence factor (VF) from pathogens produce cytokine that activates ISC proliferation and differentiation for tissue turnover.


Reference

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