华大基因研究院Yinqi Bai等合作取得新进展。他们研究开发了分子全息图的时空建模方法。相关研究成果2024年11月11日在线发表于《细胞》杂志上。

据介绍，量化胚胎发生过程中的时空动态对于理解先天性疾病至关重要。

研究人员开发了Spateo(https://github.com/aristoteo/spateo-release)，一个3D时空建模框架，并将其应用于E9.5和E11.5的3D小鼠胚胎发生图谱，捕获了800万个细胞。Spateo能够实现可扩展、部分、非刚性对齐、多层细化和网格校正，以创建整个胚胎的分子全息图。

它引入了数字化方法来揭示从亚细胞到整个器官的多层次生物学，确定了沿新兴3D结构正交轴的表达梯度，例如中脑-后脑边界（MHB）等次级组织者。Spateo进一步联合模拟细胞间和细胞内的相互作用，以剖析三维结构中的信号景观，包括丘脑内的限制带（ZLI）。

最后，Spateo引入了细胞迁移的“形态计量向量场”，并整合了空间微分几何，揭示了不对称小鼠心脏器官发生等背后的分子程序，将宏观变化与分子动力学联系起来。因此，Spateo能够在3D空间中随着时间的推移，在分子水平上研究器官生态学。

附：英文原文

Title: Spatiotemporal modeling of molecular holograms

Author: Xiaojie Qiu, Daniel Y. Zhu, Yifan Lu, Jiajun Yao, Zehua Jing, Kyung Hoi Min, Mengnan Cheng, Hailin Pan, Lulu Zuo, Samuel King, Qi Fang, Huiwen Zheng, Mingyue Wang, Shuai Wang, Qingquan Zhang, Sichao Yu, Sha Liao, Chao Liu, Xinchao Wu, Yiwei Lai, Shijie Hao, Zhewei Zhang, Liang Wu, Yong Zhang, Mei Li, Zhencheng Tu, Jinpei Lin, Zhuoxuan Yang, Yuxiang Li, Ying Gu, David Ellison, Ao Chen, Longqi Liu, Jonathan S. Weissman, Jiayi Ma, Xun Xu, Shiping Liu, Yinqi Bai

Issue&Volume: 2024-11-11

Abstract: Quantifying spatiotemporal dynamics during embryogenesis is crucial for understanding congenital diseases. We developed Spateo (https://github.com/aristoteo/spateo-release), a 3D spatiotemporal modeling framework, and applied it to a 3D mouse embryogenesis atlas at E9.5 and E11.5, capturing eight million cells. Spateo enables scalable, partial, non-rigid alignment, multi-slice refinement, and mesh correction to create molecular holograms of whole embryos. It introduces digitization methods to uncover multi-level biology from subcellular to whole organ, identifying expression gradients along orthogonal axes of emergent 3D structures, e.g., secondary organizers such as midbrain-hindbrain boundary (MHB). Spateo further jointly models intercellular and intracellular interaction to dissect signaling landscapes in 3D structures, including the zona limitans intrathalamica (ZLI). Lastly, Spateo introduces “morphometric vector fields” of cell migration and integrates spatial differential geometry to unveil molecular programs underlying asymmetrical murine heart organogenesis and others, bridging macroscopic changes with molecular dynamics. Thus, Spateo enables the study of organ ecology at a molecular level in 3D space over time.

DOI: 10.1016/j.cell.2024.10.011

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01159-0