小柯机器人

美国宾夕法尼亚大学Guo-li Ming研究小组的最新研究利用人诱导多能干细胞产生了下丘脑弓状类器官。2021年5月6日，国际学术期刊《细胞-干细胞》在线发表了这一成果。

研究人员利用人诱导多能干细胞（iPSCs）生成的弧形类器官（ARCOs）模拟了下丘脑弓状核的生成轨迹。ARCO单细胞RNA测序显示了不同弓形细胞类型间的显著分子异质性，基于新生儿下丘脑单核转录组的机器学习辅助分析进一步揭示了人弓形核的分子特征。

研究人员还探究了由Prader-Willi综合征（PWS）患者iPSC产生的ARCO。这些类器官表现出异常的分化和转录组特征，类似于PWS患者出生后的下丘脑，这表明细胞分化不足加剧了炎症反应。因此，患者iPSC衍生的ARCOs代表了一种潜在的实验模型，可用于研究早期人类弓形发育过程中特定于细胞核的特征和与疾病相关的机制。

研究人员表示，人脑类器官是研究人脑发育和疾病特征的卓越平台。现有的类器官模型不能解析精细的大脑区域，例如下丘脑中的不同核。

附：英文原文

Title: Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells

Author: Wei-Kai Huang, Samuel Zheng Hao Wong, Sarshan R. Pather, Phuong T.T. Nguyen, Feng Zhang, Daniel Y. Zhang, Zhijian Zhang, Lu Lu, Wanqi Fang, Luyun Chen, Analiese Fernandes, Yijing Su, Hongjun Song, Guo-li Ming

Issue&Volume: 2021-05-06

Abstract: Human brain organoids represent remarkable platforms for recapitulating features ofhuman brain development and diseases. Existing organoid models do not resolve finebrain subregions, such as different nuclei in the hypothalamus. We report the generationof arcuate organoids (ARCOs) from human induced pluripotent stem cells (iPSCs) tomodel the development of the human hypothalamic arcuate nucleus. Single-cell RNA sequencingof ARCOs revealed significant molecular heterogeneity underlying different arcuatecell types, and machine learning-aided analysis based on the neonatal human hypothalamussingle-nucleus transcriptome further showed a human arcuate nucleus molecular signature.We also explored ARCOs generated from Prader-Willi syndrome (PWS) patient iPSCs. Theseorganoids exhibit aberrant differentiation and transcriptomic dysregulation similarto postnatal hypothalamus of PWS patients, indicative of cellular differentiationdeficits and exacerbated inflammatory responses. Thus, patient iPSC-derived ARCOsrepresent a promising experimental model for investigating nucleus-specific featuresand disease-relevant mechanisms during early human arcuate development.

DOI: 10.1016/j.stem.2021.04.006

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00163-6

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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