Intestinal Regeneration: Regulation by the Microenvironment

Dev Cell. 2020 Aug 24;54(4):435-446. doi: 10.1016/j.devcel.2020.07.009.

Abstract

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.

Keywords: Lgr5; cellular plasticity; colon; dedifferentiation; epithelial damage; immune cells; intestine; mesenchymal cells; niche; stem cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyltransferases
  • Cell Cycle Proteins / genetics
  • Cell Dedifferentiation / genetics*
  • Cell Lineage / genetics
  • Cellular Microenvironment / genetics
  • Humans
  • Intestines / cytology
  • Intestines / growth & development*
  • Receptors, Notch / genetics
  • Regeneration / genetics*
  • Stem Cells / cytology*
  • Transcription Factors / genetics
  • Wnt Signaling Pathway / genetics

Substances

  • Cell Cycle Proteins
  • Receptors, Notch
  • Transcription Factors
  • YY1AP1 protein, human
  • Acyltransferases
  • TAFAZZIN protein, human