Chapter 7 - Induced pluripotent stem cells for studying genetic autonomic disorders

Abstract

A multitude of studies have used stem cell technology to model diseases in vitro; however, only a handful have reported findings of the autonomic nervous system (ANS). The ANS is part of the peripheral nervous system (PNS) and composed of different divisions, such as the parasympathetic, sympathetic, and enteric nervous system. Neurons from these divisions are responsible for the transmission of signals from the central nervous system (CNS) to the rest of the body, and they also aid in proper gastrointestinal (GI) function and regulation. During development, ANS neurons arise from the embryonic neural crest (NC) and differentiate based on distinct genetic and molecular signaling cascades; disruption to these during development can lead to life-threatening diseases. Similarly, harm from physical injury can initiate ANS disorders. While there are various ANS diseases to study, to date the molecular mechanisms and specific genetic background of patients with Familial dysautonomia (FD) and Hirschsprung's disease (HD) have been studied through human pluripotent stem cell (hPSC) technology. hPSC's potential to be differentiated into any cell type within the body makes them a powerful tool for advancing the understanding of genetic diseases of the ANS. Here, we review the anatomy, embryonic development, and importance of the ANS and how stem cell technology has been used to study and model genetic diseases in the ANS in addition to how it can be applied to other diseases in the future.