Overview of Methods to Differentiate Sympathetic Neurons from Human Pluripotent Stem Cells

Abstract

Sympathetic neurons are crucial for maintenance of body homeostasis and regulation of all organs. Diseases can arise from malfunction of sympathetic neurons, including malignancies, hypertension, and genetic disorders. Human pluripotent stem cells (hPSCs) allow modeling of human diseases and the indepth study of pathologies of specific cell types associated with such disorders. Advances in the ability to differentiate hPSCs in vitro has allowed the generation of specific cell types such as sympathetic neurons, which provides the novel opportunity to study diseases affecting the sympathetic nervous system in the human context. Here, we compare selected recent publications that have achieved the goal of generating sympathetic neurons from hPSCs. We discuss strengths and weaknesses of each approach and debate future improvements and the next steps for using these neurons to better our understanding of sympathetic neuron disorders and their treatments. C 2019 by John Wiley & Sons, Inc.Keywords: human pluripotent stem cells r neural crest r neuromesodermal progenitor r peripheral nervous system r sympathetic neurons r sympathoadrenal progenitor

Protocol for generating postganglionic sympathetic neurons using human pluripotent stem cells for electrophysiological and functional assessments

“…Overall, this protocol provides an efficient method to differentiate postganglionic symNs. Compared with other similar protocols, 8 , 9 , 10 , 11 , 12 , 13 our NC differentiation is free of FACS sorting process (which is needed in the protocol by Oh et al. 11 ), and can be cryopreserved (which is only described by Kirino et al.…”

Stem Cell‐Based Models for Studying the Effects of Cancer and Cancer Therapies on the Peripheral Nervous System

“…Protocols to derive sympathetic neurons or cultures containing both sympathetic and parasympathetic nerves from hPSCs are now available and, therefore, may be used to help bridge this gap in knowledge. [20,21] For example, following two weeks of autonomic neuron induction and one month of neuronal maturation, bona fide sympathetic and parasympathetic neurons can be derived that express key lineage identity markers which have been successfully utilized to uncover biological underpinnings of Familial Dysautonomia. [21] Utilizing this differentiation protocol in the context of prostate cancer neurobiology research, the parasympathetic and sympathetic neurons could be sorted prior to experimentation in order to study the direct role of each PNS population in prostate cancer.…”