小柯机器人

新方法可诱导人多能干细胞形成纹状体类器官
2020-12-04 13:30

美国斯坦福大学Sergiu P. Paca课题组的最新研究诱导人多能干细胞产生了纹状体类器官和皮质-纹状体类器官装配体。 2020年12月3日,国际学术期刊《自然-生物技术》发表了这一成果。

为了研究人皮质纹状体途径及其功能障碍如何导致神经精神疾病,研究人员研发了一种新方法,其可将人多能干细胞诱导为区域特异性的大脑类器官,该类器官类似于发育中的人纹状体,并包括具有中等电活性的多刺神经元。随后,研究人员在三维培养基中将这些类器官与大脑皮质类器官装配在一起,形成皮质-纹状体类器官装配体。

利用病毒跟踪和功能分析完整或切片类器官装配体,研究表明皮质神经元将轴突映射发送到纹状体类器官并形成突触连接。中棘状神经元在组装后成熟,并在光遗传刺激皮层神经元后显示钙活性。

此外,研究人员从由22q13.3号染色体缺失引起的神经发育障碍患者中获得了皮质纹状体的类器官装配体,并捕获了与钙离子活性相关的疾病缺陷,表明该方法有助于使用患者来源的细胞研究皮质纹状体的发育和功能性装配体。

据了解,皮质纹状体映射是前脑电路调控动机行为的关键组成部分。

附:英文原文

Title: Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells

Author: Yuki Miura, Min-Yin Li, Fikri Birey, Kazuya Ikeda, Omer Revah, Mayuri Vijay Thete, Jin-Young Park, Alyssa Puno, Samuel H. Lee, Matthew H. Porteus, Sergiu P. Paca

Issue&Volume: 2020-12-03

Abstract: Cortico-striatal projections are critical components of forebrain circuitry that regulate motivated behaviors. To enable the study of the human cortico-striatal pathway and how its dysfunction leads to neuropsychiatric disease, we developed a method to convert human pluripotent stem cells into region-specific brain organoids that resemble the developing human striatum and include electrically active medium spiny neurons. We then assembled these organoids with cerebral cortical organoids in three-dimensional cultures to form cortico-striatal assembloids. Using viral tracing and functional assays in intact or sliced assembloids, we show that cortical neurons send axonal projections into striatal organoids and form synaptic connections. Medium spiny neurons mature electrophysiologically following assembly and display calcium activity after optogenetic stimulation of cortical neurons. Moreover, we derive cortico-striatal assembloids from patients with a neurodevelopmental disorder caused by a deletion on chromosome 22q13.3 and capture disease-associated defects in calcium activity, showing that this approach will allow investigation of the development and functional assembly of cortico-striatal connectivity using patient-derived cells. 

DOI: 10.1038/s41587-020-00763-w

Source: https://www.nature.com/articles/s41587-020-00763-w

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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