小柯机器人

美国耶鲁医学院In-Hyun Park和上海科技大学Yangfei Xiang共同合作，近期取得重要工作进展。他们研究培养出了具有丘脑网状核的腹侧化人丘脑类器官。相关研究成果2023年4月4日在线发表于《细胞—干细胞》杂志上。

据介绍，人脑类器官为模拟人脑发育和病理学的几个方面提供了独特的平台。然而，目前的大脑类器官系统大多缺乏再现具有次区域特征的精细大脑结构发展的分辨率，包括丘脑中功能不同的细胞核。

研究人员报道了一种将人类胚胎干细胞（hESC）转化为具有转录多样细胞核身份的腹侧丘脑类器官（vThO）的方法。值得注意的是，单细胞RNA测序揭示了以前未实现的丘脑模式，其具有丘脑网状核（TRN）特征，即位于腹侧丘脑的GABA能核。使用vThO，研究人员探索了TRN特异性、疾病相关基因补丁含结构域1（PTCHD1）和受体酪氨酸蛋白激酶（ERBB4）在人类丘脑发育过程中的功能。PTCHD1或ERBB4的扰动损害了vThO的神经元功能，尽管不会影响整个丘脑谱系的发育。

总之，vThO共同提供了一个实验模型，用于理解人脑丘脑中细胞核的特异性发育和病理。

附：英文原文

Title: Generation of ventralized human thalamic organoids with thalamic reticular nucleus

Author: Ferdi Ridvan Kiral, Bilal Cakir, Yoshiaki Tanaka, Jonghun Kim, Woo Sub Yang, Fabien Wehbe, Young-Jin Kang, Mei Zhong, Gizem Sancer, Sang-Hun Lee, Yangfei Xiang, In-Hyun Park

Issue&Volume: 2023-04-04

Abstract: Human brain organoids provide unique platforms for modeling several aspects of humanbrain development and pathology. However, current brain organoid systems mostly lackthe resolution to recapitulate the development of finer brain structures with subregionalidentity, including functionally distinct nuclei in the thalamus. Here, we reporta method for converting human embryonic stem cells (hESCs) into ventral thalamic organoids(vThOs) with transcriptionally diverse nuclei identities. Notably, single-cell RNAsequencing revealed previously unachieved thalamic patterning with a thalamic reticularnucleus (TRN) signature, a GABAergic nucleus located in the ventral thalamus. UsingvThOs, we explored the functions of TRN-specific, disease-associated genes patcheddomain containing 1 (PTCHD1) and receptor tyrosine-protein kinase (ERBB4) during humanthalamic development. Perturbations in PTCHD1 or ERBB4 impaired neuronal functionsin vThOs, albeit not affecting the overall thalamic lineage development. Together,vThOs present an experimental model for understanding nuclei-specific developmentand pathology in the thalamus of the human brain.

DOI: 10.1016/j.stem.2023.03.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00078-4

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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