系统scRNA-seq筛选分析神经类器官对形态因子的反应，这一成果由苏黎世联邦理工学院Barbara Treutlein团队经过不懈努力而取得。相关论文发表在2025年12月15日出版的《自然—方法学》杂志上。

在这里，研究组详细调查了形态诱导对人类神经类器官区域规格的影响，主题是多路单细胞转录组筛选。该课题组人员发现，形成因子的时间、浓度和组合强烈影响类器官细胞类型和区域组成，细胞系和神经诱导方法影响对给定形态因子条件的反应。该课题组人员在微流控芯片中应用浓度梯度或在多孔板中增加静态浓度，并在每种情况下观察到不同的模式动力学。总之，该团队提供了神经谱系规范的详细研究，结合深度学习模型，可以预测人类干细胞系统的分化结果。

据介绍，形态原在体内将神经上皮细胞的命运导向离散的区域特征。神经类器官通过形态素暴露为研究神经区域化提供了模型；然而，该课题组研究人员缺乏对发育中的人类神经上皮如何响应形态发生线索的全面调查。

附：英文原文

Title: Systematic scRNA-seq screens profile neural organoid response to morphogens

Author: Sanchs-Calleja, Ftima, Azbukina, Nadezhda, Jain, Akanksha, He, Zhisong, Okamoto, Ryoko, Rusimbi, Charlotte, Rifes, Pedro, Rathore, Gaurav Singh, Santel, Malgorzata, Janssens, Jasper, Seimiya, Makiko, Eisinger, Benedikt, Fleck, Jonas Simon, Kirkeby, Agnete, Camp, J. Gray, Treutlein, Barbara

Issue&Volume: 2025-12-15

Abstract: Morphogens direct neuroepithelial fates toward discrete regional identities in vivo. Neural organoids provide models for studying neural regionalization through morphogen exposure; however, we lack a comprehensive survey of how the developing human neuroepithelium responds to morphogen cues. Here we produce a detailed survey of morphogen-induced effects on the regional specification of human neural organoids using multiplexed single-cell transcriptomic screens. We find that the timing, concentration and combination of morphogens strongly influence organoid cell-type and regional composition, and that cell line and neural induction method impact the response to a given morphogen condition. We apply concentration gradients in microfluidic chips or increasing static concentrations in multi-well plates and observe different patterning dynamics in each scenario. Altogether, we provide a detailed resource on neural lineage specification that, in combination with deep learning models, can enable the prediction of differentiation outcomes in human stem-cell-based systems.

DOI: 10.1038/s41592-025-02927-5

Source: https://www.nature.com/articles/s41592-025-02927-5