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Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids
Cell and Tissue Research ( IF 3.6 ) Pub Date : 2020-07-31 , DOI: 10.1007/s00441-020-03249-y
Lisa M Smits 1 , Stefano Magni 1 , Kaoru Kinugawa 2 , Kamil Grzyb 1 , Joachim Luginbühl 3 , Sonia Sabate-Soler 1 , Silvia Bolognin 1 , Jay W Shin 3 , Eiichiro Mori 2 , Alexander Skupin 1, 4 , Jens C Schwamborn 1
Affiliation  

Human stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulate in vitro the organization and function of a respective organ or part of an organ. Human midbrain organoids (hMOs) have been described to contain midbrain-specific dopaminergic neurons that release the neurotransmitter dopamine. However, the human midbrain contains also additional neuronal cell types, which are functionally interacting with each other. Here, we analysed hMOs at high-resolution by means of single-cell RNA sequencing (scRNA-seq), imaging and electrophysiology to unravel cell heterogeneity. Our findings demonstrate that hMOs show essential neuronal functional properties as spontaneous electrophysiological activity of different neuronal subtypes, including dopaminergic, GABAergic, glutamatergic and serotonergic neurons. Recapitulating these in vivo features makes hMOs an excellent tool for in vitro disease phenotyping and drug discovery.

中文翻译:

单细胞转录组学揭示了人类中脑特异性类器官中的多种神经元细胞类型

人类干细胞衍生的类器官具有模拟生理和病理过程的巨大潜力。它们在体外概括了各个器官或器官的一部分的组织和功能。人类中脑类器官 (hMO) 已被描述为包含释放神经递质多巴胺的中脑特异性多巴胺能神经元。然而,人类中脑还包含额外的神经元细胞类型,它们在功能上相互作用。在这里,我们通过单细胞 RNA 测序 (scRNA-seq)、成像和电生理学以高分辨率分析 hMO,以揭示细胞异质性。我们的研究结果表明,hMO 显示出基本的神经元功能特性,如不同神经元亚型的自发电生理活动,包括多巴胺能、GABA 能、谷氨酸能和血清素能神经元。概括这些体内特征使 hMO 成为体外疾病表型分析和药物发现的绝佳工具。
更新日期:2020-07-31
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