hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids
hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids
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DOI：
10.1016/j.stem.2018.12.015
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发表时间：
2019-03-07
期刊：
影响因子：
23.9
通讯作者：
Park, In-Hyun
中科院分区：
文献类型：
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作者：
Xiang, Yangfei;Tanaka, Yoshiaki;Park, In-Hyun
人脑类器官技术迅速发展，有助于研究人脑发育和疾病。这些努力主要集中在产生端脑，因为它与各种前脑疾病直接相关。尽管它作为皮层和外周组织之间的中继枢纽很重要，但人类丘脑的三维（3D）类器官模型的研究尚未得到探索。在这里，我们描述了一种将人类胚胎干细胞（hESCs）分化为丘脑类器官（hThOs）的方法，后者专门概括了丘脑的发育。单细胞RNA测序揭示了不同丘脑谱系的形成，这与端脑的命运不同。重要的是，我们开发了一个3D系统，通过融合代表发育中的丘脑或皮层的两个不同区域特异性器官，来创建丘脑和皮层之间的相互投影。我们的研究为理解人类丘脑发育和模拟回路组织及大脑相关疾病提供了一个平台。
Human brain organoid techniques have rapidly advanced to facilitate investigating human brain development and diseases. These efforts have largely focused on generating telencephalon due to its direct relevance in a variety of forebrain disorders. Despite its importance as a relay hub between cortex and peripheral tissues, the investigation of three-dimensional (3D) organoid models for the human thalamus has not been explored. Here, we describe a method to differentiate human embryonic stem cells (hESCs) to thalamic organoids (hThOs) that specifically recapitulate the development of thalamus. Single-cell RNA sequencing revealed a formation of distinct thalamic lineages, which diverge from telencephalic fate. Importantly, we developed a 3D system to create the reciprocal projections between thalamus and cortex by fusing the two distinct region-specific organoids representing the developing thalamus or cortex. Our study provides a platform for understanding human thalamic development and modeling circuit organizations and related disorders in the brain.