具有细胞核特异性的大脑类器官为更高分辨率地研究人类大脑发育和疾病提供了独特的平台。尽管后脑髓质在重要的身体功能中发挥着重要作用，但它仍然缺乏体外模型，更不用说类似于特定髓质核的模型了，包括将外周感觉信号传递到丘脑的关键的三叉神经脊髓核（SpV）。在这里，我们报告了一种将人类多能干细胞分化为类似于髓质后脑背侧区域的区域特异性脑类器官的方法。重要的是，类器官特别再现了源自背髓质的 SpV 的发育。我们还开发了一种类器官系统，通过融合这些类器官，即人类髓质 SpV 样类器官 (hmSpVOs) 和代表丘脑的类器官 (hThOs)，在 SpV 和丘脑之间创建三叉丘脑投影。我们的研究为理解 SpV 发育、基于核的回路组织以及人脑相关疾病提供了一个平台。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Brain organoids with nucleus-specific identities provide unique platforms for studying human brain development and diseases at a finer resolution. Despite its essential role in vital body functions, the medulla of the hindbrain has seen a lack of in vitro models, let alone models resembling specific medullary nuclei, including the crucial spinal trigeminal nucleus (SpV) that relays peripheral sensory signals to the thalamus. Here, we report a method to differentiate human pluripotent stem cells into region-specific brain organoids resembling the dorsal domain of the medullary hindbrain. Importantly, organoids specifically recapitulated the development of the SpV derived from the dorsal medulla. We also developed an organoid system to create the trigeminothalamic projections between the SpV and the thalamus by fusing these organoids, namely human medullary SpV-like organoids (hmSpVOs), with organoids representing the thalamus (hThOs). Our study provides a platform for understanding SpV development, nucleus-based circuit organization, and related disorders in the human brain.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.