PDF(Pubmed)
Abstract：
Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including \"rest-and-digest.\" ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors. We employ these neurons (1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathy in the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunction during SARS-CoV-2 infection, (4) to model the autoimmune disease Sjögren\'s syndrome (SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during development and promote WAT maturation. Our model system could become instrumental for future disease modeling and drug discovery studies, as well as for human developmental studies.
摘要：
自主副交感神经元（parsymNs）控制无意识的身体反应，包括“休息和消化”。“ParsymN神经支配对器官发育很重要，parasymN功能障碍是自主神经病变的标志。然而,由于缺乏模型系统，人类的parasymN功能和功能障碍被广泛研究。人类多能干细胞（hPSC）衍生的神经元可以作为通用平台填补这一空白。这里,我们开发了一种分化范式，详细说明了从雪旺氏细胞祖细胞衍生出功能性人类parasymNs。我们使用这些神经元（1）来评估人类自主神经系统（ANS）的发育，(2)建立遗传性家族性自主神经障碍(FD)神经病变模型,(3)在SARS-CoV-2感染过程中表现出副群功能障碍，(4)建立自身免疫性疾病干燥综合征(SS)模型，和（5）显示，在发育过程中，顺式神经支配白色脂肪细胞（WATs）并促进WAT成熟。我们的模型系统可以成为未来疾病建模和药物发现研究的工具，以及人类发展研究。
