团队表示，"MultiCell"是首个能在多细胞自组装过程中，实现各类细胞行为单细胞精度预测的算法。鉴 于其可捕捉细胞动力学上存在的微妙差异，未来将助力早期诊断或药物筛选。 美国麻省理工学院、密歇根大学和东北大学联合团队在最新《自然·方法》杂志上发表论文，介绍了一 种名为"MultiCell"的几何深度学习模型。该模型首次实现了在单细胞分辨率下，预测果蝇胚胎发育过程 中，每个细胞在每分钟的行为变化。未来可在此基础上设计出通用的多细胞发育预测模型，构建"数字 胚胎"，用于药物筛选甚至指导人工组织设计。 一个胚胎如何从一团细胞变成有头有尾、有器官的完整生命体，是发育生物学领域持续百年的核心谜 题。虽然科学家早已知道细胞会分裂、移动、折叠，但具体到某一个细胞在下一分钟会有什么动态行 为，却一直难以预测。 模型采用四维全胚胎数据进行训练和测试，这些数据具有亚微米级分辨率和较高的帧率，每个胚胎包含 约5000个被标注边界和细胞核的细胞。在测试中，模型不仅能判断细胞是否会发生特定行为，还能精确 预测行为发生的时间是几分钟后。团队将这一方法与"阿尔法折叠"预测的蛋白质结构相类比：阿尔法折 叠是从氨基酸序列推断蛋白质三维结构 ...

Core Viewpoint - The article discusses a significant advancement in understanding early organogenesis in mouse embryos through the creation of a 3D "digital embryo" using single-cell resolution techniques, which provides insights into organ formation and potential mechanisms of congenital malformations [2][10]. Group 1: Early Organogenesis - Early organogenesis is a critical phase in embryonic development characterized by extensive cell fate determination to initiate organ formation, while also being highly susceptible to developmental defects [4]. - At approximately day 7.5 of embryonic development (E7.5), mouse embryos undergo significant morphological changes, marked by the emergence of key structures such as the heart tube and primitive gut [4]. - The complex process of organ formation relies on precise cell migration, localization, and differentiation, regulated by spatiotemporal gene expression patterns and intricate signaling pathways [4][5]. Group 2: Research Methodology - The research team combined spatial transcriptomics methods (Stereo-seq) with cell segmentation techniques to analyze 285 continuous slices from six embryos at early organogenesis stages (E7.5-E8.0), generating a spatial transcriptomic map at single-cell resolution [6]. - A visualization platform named SEU-3D was developed to reconstruct the 3D "digital embryo," accurately reflecting gene expression patterns and cell states in the native embryonic environment [7]. Group 3: Findings and Implications - The research delineated spatial cell maps of endoderm and mesoderm derivatives, revealing complex signaling networks across germ layers and cell types [8]. - A region known as the progenitor determination zone (PDZ) was identified at the anterior interface of the embryo-extrembryonic region at E7.75, indicating coordinated signaling during heart progenitor formation [8]. - The results collectively establish a comprehensive spatiotemporal embryonic atlas at single-cell resolution, accompanied by a network-based exploration tool for navigating spatial gene expression and signaling networks, paving the way for deeper studies into embryonic development and diseases [10].