Liu Xuanqi, Duan Wanxin, Qiu Yuyang, Li Ruyi, Song Yuanlin, Wang Xiangdong
Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, China.
Shanghai Institute of Clinical Bioinformatics, Shanghai, China.
Clin Transl Med. 2025 Sep;15(9):e70470. doi: 10.1002/ctm2.70470.
Spatiotemporal distributions of intracellular elements (e.g., small molecules, proteins and organelles) dynamically altered in response to extracellular stimuli and pathogens, regulating those element movements, remodelling, and functions independently of mere changes in element abundance. To distinguish from conventional one- or two-dimensional spatialization, we define the precise three-dimensional localisation and interactions of intra- and extracellular elements at the single cell level as the "stereologically spatiotemporal cell" (SST-cell). For example, the three-dimensional construction of chromosomes ensures their proper formation and spatial positioning, facilitates the recruitment of regulatory factors, and underlies the mechanisms by which these factors maintain chromatin architecture. A large number of intracellular organelles and sub-organelles, along with their intercommunications, decide cellular biological types, subtype specification and type-specific functions. With the development of Stereo-Cell and Stereo-seq, the measurement of spatial SST-cell omics probably enables the detailed dissection of spatial heterogeneity among different cell subtypes and states, as well as their intercellular communications. Furthermore, the new approach of single SST-cell drug screening will be innovated for developing the new generation of clinical precision therapies.
细胞内成分(如小分子、蛋白质和细胞器)的时空分布会根据细胞外刺激和病原体动态改变,独立于成分丰度的单纯变化来调节这些成分的移动、重塑和功能。为了与传统的一维或二维空间化区分开来,我们将单细胞水平上细胞内和细胞外成分的精确三维定位及相互作用定义为“立体时空细胞”(SST细胞)。例如,染色体的三维结构确保其正确形成和空间定位,促进调控因子的募集,并构成这些因子维持染色质结构机制的基础。大量细胞内细胞器和亚细胞器及其相互通讯决定了细胞的生物学类型、亚型特异性和类型特异性功能。随着立体细胞和立体测序技术的发展,空间SST细胞组学的测量可能有助于详细剖析不同细胞亚型和状态之间的空间异质性及其细胞间通讯。此外,将创新单细胞SST细胞药物筛选的新方法,以开发新一代临床精准疗法。