通过单细胞转录组偶联模式筛选的人类神经元亚型编程，这一成果由
研究团队调节发育信号通路并结合TF过表达来探索多能干细胞产生的神经元亚型谱。研究人员筛选了480种与TF诱导耦合的形态因子信号调节，这些信号调节具有多重单细胞转录组读数。对70万个细胞的分析确定了沿神经管发育轴分布的各种兴奋性和抑制性神经元。在TF过表达之前对神经祖细胞进行模式化，通过激活在原代组织对应物中活跃的调控，扩大了神经元的多样性。他们的方法为编程不同的人类细胞亚型以及研究合作信号如何驱动神经元命运提供了一种策略。
研究人员表示，人类神经元编程通过转录因子（TF）过表达模型神经元分化和疾病。然而，在体外可编程的神经元亚型的多样性仍未得到解决。
附：英文原文
Title: Human neuron subtype programming via single-cell transcriptome-coupled patterning screens
Author: Hsiu-Chuan Lin, Jasper Janssens, Benedikt Eisinger, Philipp Hornauer, Ann-Sophie Kroell, Malgorzata Santel, Maria Pascual-Garcia, Ryoko Okamoto, Kyriaki Karava, Zhisong He, Marthe Priouret, Manuel Schrter, J. Gray Camp, Barbara Treutlein
Issue&Volume: 2025-07-10
Abstract: Human neurons programmed through transcription factor (TF) overexpression model neuronal differentiation and disease. However, the diversity of neuronal subtypes programmable in vitro remains unresolved. We modulated developmental signaling pathways combined with TF overexpression to explore the spectrum of neuron subtypes generated from pluripotent stem cells. We screened 480 morphogen signaling modulations coupled with TF induction using a multiplexed single-cell transcriptomic readout. Analysis of 700,000 cells identified diverse excitatory and inhibitory neurons patterned along the developmental axes of the neural tube. Patterning neural progenitors prior to TF overexpression expanded neuronal diversity by enabling access to regulons active in primary tissue counterparts. Our approach provides a strategy for programming diverse human cell subtypes as well as investigating how cooperative signaling drives neuronal fate.
DOI: adn6121
Source: https://www.science.org/doi/10.1126/science.adn6121