Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids.
Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids.
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DOI：
10.1007/s00441-020-03249-y
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发表时间：
2020-12
影响因子：
3.6
通讯作者：
Schwamborn JC
中科院分区：
文献类型：
--
作者：
Smits LM;Magni S;Kinugawa K;Grzyb K;Luginbühl J;Sabate-Soler S;Bolognin S;Shin JW;Mori E;Skupin A;Schwamborn JC
人类干细胞衍生的类器官在模拟生理和病理过程方面具有巨大的潜力。它们在体外概括了各自器官或器官部分的组织和功能。人类中脑类器官（hMOs）含有释放神经递质多巴胺的中脑特异性多巴胺能神经元。然而，人类的中脑也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）、成像和电生理学等手段对hMOs进行了高分辨率分析，以揭示细胞异质性。我们的研究结果表明，hMOs具有基本的神经元功能特性，作为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hMOs成为体外疾病表型和药物发现的绝佳工具。本文的在线版本（10.1007/s00441-020-03249-y）包含补充材料，授权用户可使用。
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. The online version of this article (10.1007/s00441-020-03249-y) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
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影响因子：
17.1
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Cooper O;Seo H;Andrabi S;Guardia-Laguarta C;Graziotto J;Sundberg M;McLean JR;Carrillo-Reid L;Xie Z;Osborn T;Hargus G;Deleidi M;Lawson T;Bogetofte H;Perez-Torres E;Clark L;Moskowitz C;Mazzulli J;Chen L;Volpicelli-Daley L;Romero N;Jiang H;Uitti RJ;Huang Z;Opala G;Scarffe LA;Dawson VL;Klein C;Feng J;Ross OA;Trojanowski JQ;Lee VM;Marder K;Surmeier DJ;Wszolek ZK;Przedborski S;Krainc D;Dawson TM;Isacson O
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4.6
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4.6
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Garcia-Dominguez, M;Poquet, C;Charnay, P
通讯作者：
Charnay, P
影响因子：
64.5
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通讯作者：
Ming GL