The digestive system has a key role in maintaining body homeostasis through different physiological functions, including the coordinated contractility patterns necessary for the progression of the ingested food along the gastrointestinal (GI) tract, the secretion of different substances, and the uptake of nutrients. In order to, fulfil this variety of fundamental activities, the GI tract is tightly tuned, with the intrinsic innervation of the gut, e.g., the enteric nervous system (ENS), being one of the most prominent regulatory mechanisms. Several morpho-functional techniques are currently available to study the different enteric components and the complex network of cells giving rise to the ENS and their pathophysiological counterparts in patients.

Recent technological advances have improved our understanding of the complexity of ENS and related enteric neuromyopathies. Moreover, researchers have developed methods to obtain three-dimensional intestinal organ cultures (organoids) by differentiating human induced pluripotent stem cells (iPSCs). Developing transplantable intestinal tissues that carry all the functional physiological components is also possible. These technologies suggest that stem cell-based therapies can be foreseen for treating enteric neuromyopathies. Another frontier in ENS research is the development of technologies for single-cell molecular profiling to evaluate the localization, differentiation, and evolution across species of different classes of enteric cells. These technological approaches will be discussed and presented in this issue.