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来源于人类多能干细胞的副交感神经元可模拟人类疾病和发育过程
作者:小柯机器人 发布时间:2024/4/13 17:12:48

美国佐治亚大学Nadja Zeltner课题组发现,来源于人类多能干细胞的副交感神经元可模拟人类疾病和发育过程。2024年4月11日,国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员开发了一种分化范式,详细说明了从许旺细胞祖细胞衍生出功能性人类自主副交感神经元(parasymN)的过程。研究人员利用这些神经元(1)评估人类自主神经系统(ANS)的发育;(2)模拟遗传性疾病家族性自律神经失调症(FD)的神经病变;(3)展示SARS-CoV-2感染期间parasymN的功能障碍;(4)模拟自身免疫性疾病干燥综合征(SS);以及(5)展示parasymN在发育过程中支配白色脂肪细胞(WAT)并促进WAT的成熟。这个模型系统将有助于未来的疾病建模、药物发现研究以及人类发育研究。

据悉,parasymN控制着身体的无意识反应,包括“休息和消化”。副交感神经支配对器官的发育非常重要,而副交感神经功能障碍是自律神经病变的标志。然而,由于缺乏模型系统,对人类副交感神经功能和功能障碍的研究远远不够。人类多能干细胞(hPSC)衍生的神经元可作为一个多功能平台填补这一空白。

附:英文原文

Title: Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development

Author: Hsueh-Fu Wu, Kenyi Saito-Diaz, Chia-Wei Huang, Jessica L. McAlpine, Dong Eun Seo, D. Sumner Magruder, Mohamed Ishan, Harrison C. Bergeron, William H. Delaney, Fabio R. Santori, Smita Krishnaswamy, Gerald W. Hart, Ya-Wen Chen, Robert J. Hogan, Hong-Xiang Liu, Natalia B. Ivanova, Nadja Zeltner

Issue&Volume: 2024-04-11

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, parasymNfunction and dysfunction in humans are vastly understudied due to the lack of a modelsystem. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as aversatile platform. Here, we developed a differentiation paradigm detailing the derivationof functional human parasymNs from Schwann cell progenitors. We employ these neurons(1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathyin the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunctionduring SARS-CoV-2 infection, (4) to model the autoimmune disease Sjgren’s syndrome(SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during developmentand promote WAT maturation. Our model system could become instrumental for futuredisease modeling and drug discovery studies, as well as for human developmental studies.

DOI: 10.1016/j.stem.2024.03.011

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00092-4

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx

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