The multiple roles of enteric glial cells in intestinal homeostasis and regeneration

The gastrointestinal tract is innervated by the enteric nervous system (ENS), a complex network of neurons and glial cells, also called the second brain. Enteric glial cells, one of the major cell types in the ENS, are located throughout the entire gut wall. Accumulating evidence has demonstrated their critical requirement for gut physiology. Notably, recent studies have shown that enteric glial cells control new aspects of gut function such as regulation of intestinal stem cell behavior and immunity. In addition, the emergence of single-cell genomics technologies has revealed enteric glial cell heterogeneity and plasticity. In this review, we discuss established and emerging concepts regarding the roles of mammalian enteric glial cells and their heterogeneity in gut devel-opment, homeostasis, and regeneration.

Automated summary

The gastrointestinal tract is innervated by the enteric nervous system (ENS), also called the second brain. Enteric glial cells, a major cell type in the ENS, play critical roles in gut physiology, including the regulation of intestinal stem cells and immunity. Recent advances in single-cell genomics have revealed the heterogeneity and plasticity of enteric glial cells. This review discusses the established and emerging concepts regarding the roles of mammalian enteric glial cells in gut development, homeostasis, and regeneration.