通过神经上皮途径从人类多能干细胞生成功能性成熟交感神经元

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2024-02-15 DOI:10.1007/s12031-024-02196-5
Yubao Fan, Shanshan Huang, Fugui Li, Xiyu Zhang, Xueying Huang, Weiqiang Li, Jixiao Zeng, Weijia Wang, Jia Liu
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引用次数: 0

摘要

交感神经系统(SNS)是自律神经系统(ANS)的一个重要分支,负责调节内脏功能和各种生理过程。交感神经系统功能失调可导致各种疾病,如高血压和代谢紊乱。然而,从人体组织中获取交感神经元用于研究具有挑战性。目前的研究旨在重现人类交感神经元的发育过程,并成功建立了一个逐步、高效的体外分化方案。该方案使用化学定义的诱导培养基,促进了从人类多能干细胞(hPSCs)中生成功能性成熟交感神经元。最初,通过神经上皮细胞(NECs)和主干神经嵴干细胞(NCSCs)对每个分化阶段进行细化,从hPSCs中衍生出交感肾上腺祖细胞(SAPs)。hPSC衍生的SAPs可在体外扩增至少12次,同时保持SAP特异性转录因子的表达和神经元分化效力。在神经元成熟培养基中培养 3-4 周后,SAP 很容易产生功能性交感神经元(SymNs)。这些交感神经元表达交感神经标志物,表现出电生理特性,并分泌交感神经递质。更重要的是,我们进一步证实了源于hPSC的SymNs能有效调节体外人脂肪干细胞(ADSCs)的脂肪生成和脂质代谢。总之,我们的研究为从hPSCs产生功能性交感神经元提供了一个简单而稳健的方案,这可能是揭示SNS相关疾病机制的一个宝贵工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Generation of Functional and Mature Sympathetic Neurons from Human Pluripotent Stem Cells via a Neuroepithelial Route

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.

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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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