Modeling enteric glia development, physiology and disease using human pluripotent stem cells.

Enteric glia play an integral role in many functions of the gastrointestinal (GI) system, but they have not been characterized comprehensively compared to other cells of the gut. Enteric glia are a specialized type of neuroglia in the enteric nervous system (ENS) that support neurons and interact with other cells of the gut such as immune and epithelial cells. The ENS is diffusely spread throughout the GI tract, making it extremely difficult to access and manipulate. As a result, it has remained extremely understudied. Nevertheless, much more is known about enteric neurons than enteric glia despite the glia being 6 times more abundant in humans [1]. In the past two decades, our understanding of enteric glia has greatly expanded and their many roles in the gut have been described and reviewed elsewhere [2-5]. While the field has made substantial progress, there are still a multitude of open questions about enteric glia biology and their role in disease. Many of these questions have remained intractable due to technical limitations of currently available experimental models of the ENS. In this review, we describe the benefits and limitations of the models commonly used to study enteric glia and discuss the ways in which a human pluripotent stem cell (hPSC) derived enteric glia model could help advance the field.