Brainstem Organoids From Human Pluripotent Stem Cells
Brainstem Organoids From Human Pluripotent Stem Cells
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DOI：
10.3389/fnins.2020.00538
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发表时间：
2020-06-26
影响因子：
4.3
通讯作者：
Mori, Eiichiro
中科院分区：
文献类型：
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作者：
Eura, Nobuyuki;Matsui, Takeshi K.;Mori, Eiichiro
脑干是大脑的后部区域，由中脑、脑桥和延髓三部分组成。脑干对控制心跳、血压和呼吸至关重要，这些都是维持生命的功能，因此，脑干的损害或紊乱可能是致命的。人类多能干细胞（hPSCs）衍生的脑类器官概括了人类大脑的发育过程，有望用于中枢神经系统疾病的医学研究。然而，现有的类器官模型在人造血干细胞重现人脑发育的程度上受到限制，因此无法完全阐明影响大脑各部分（如脑干）的疾病。在这里，我们开发了一种方法来产生人类脑干类器官（hbso），包含中脑/后脑祖细胞、去甲肾上腺素能和胆碱能神经元、多巴胺能神经元和神经嵴谱系细胞。单细胞RNA序列（scRNA-seq）分析以及蛋白质组学和电生理学的证据显示，这些类器官中的细胞群与人类脑干的细胞群相似，这增加了利用hbso研究影响脑干的中枢神经系统疾病和有效药物筛选的可能性。
The brainstem is a posterior region of the brain, composed of three parts, midbrain, pons, and medulla oblongata. It is critical in controlling heartbeat, blood pressure, and respiration, all of which are life-sustaining functions, and therefore, damages to or disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate the course of human brain development and are expected to be useful for medical research on central nervous system disorders. However, existing organoid models are limited in the extent hPSCs recapitulate human brain development and hence are not able to fully elucidate the diseases affecting various components of the brain such as brainstem. Here, we developed a method to generate human brainstem organoids (hBSOs), containing midbrain/hindbrain progenitors, noradrenergic and cholinergic neurons, dopaminergic neurons, and neural crest lineage cells. Single-cell RNA sequence (scRNA-seq) analysis, together with evidence from proteomics and electrophysiology, revealed that the cellular population in these organoids was similar to that of the human brainstem, which raises the possibility of making use of hBSOs in investigating central nervous system disorders affecting brainstem and in efficient drug screenings.