Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
J Mol Neurosci. 2024 Feb 15;74(1):19. doi: 10.1007/s12031-024-02196-5.
The sympathetic nervous system (SNS) is a crucial branch of the autonomic nervous system (ANS) that is responsible for regulating visceral function and various physiological processes. Dysfunction of the SNS can lead to various diseases, such as hypertension and metabolic disorders. However, obtaining sympathetic neurons from human tissues for research is challenging. The current research aimed at recapitulating the process of human sympathetic neuron development and achieved the successful establishment of a stepwise, highly efficient in vitro differentiation protocol. This protocol facilitated the generation of functional and mature sympathetic neurons from human pluripotent stem cells (hPSCs) using a chemical-defined induction medium. Initially, each differentiation stage was refined to derive sympathoadrenal progenitors (SAPs) from hPSCs through neural epithelial cells (NECs) and trunk neural crest stem cells (NCSCs). hPSC-derived SAPs could be expanded in vitro for at least 12 passages while maintaining the expression of SAP-specific transcription factors and neuronal differentiation potency. SAPs readily generated functional sympathetic neurons (SymNs) when cultured in the neuronal maturation medium for 3-4 weeks. These SymNs expressed sympathetic markers, exhibited electrophysiological properties, and secreted sympathetic neurotransmitters. More importantly, we further demonstrated that hPSC-derived SymNs can efficiently regulate the adipogenesis of human adipose-derived stem cells (ADSCs) and lipid metabolism in vitro. In conclusion, our study provided a simple and robust protocol for generating functional sympathetic neurons from hPSCs, which may be an invaluable tool in unraveling the mechanisms of SNS-related diseases.
交感神经系统（SNS）是自主神经系统（ANS）的一个重要分支，负责调节内脏功能和各种生理过程。SNS 的功能障碍可导致各种疾病，如高血压和代谢紊乱。然而，从人体组织中获取交感神经元进行研究具有挑战性。目前的研究旨在重现人类交感神经元发育的过程，并成功建立了一个逐步的、高效的体外分化方案。该方案使用化学定义的诱导培养基，从人多能干细胞（hPSCs）中生成功能性和成熟的交感神经元。最初，每个分化阶段都经过优化，通过神经上皮细胞（NECs）和躯干神经嵴干细胞（NCSCs）从 hPSCs 中衍生出交感肾上腺祖细胞（SAPs）。hPSC 衍生的 SAPs 可以在体外至少传代 12 代，同时保持 SAP 特异性转录因子的表达和神经元分化潜能。当在神经元成熟培养基中培养 3-4 周时，SAPs 很容易生成功能性交感神经元（SymNs）。这些 SymNs 表达交感标记物，表现出电生理特性，并分泌交感神经递质。更重要的是，我们进一步证明 hPSC 衍生的 SymNs 可以有效地调节人脂肪来源干细胞（ADSCs）的成脂作用和体外脂质代谢。总之，我们的研究提供了一种从 hPSCs 生成功能性交感神经元的简单而强大的方案，这可能是揭示 SNS 相关疾病机制的宝贵工具。
