Chen Xiaoyong, Lin Shichao, You Honghai, Chen Jinyuan, Wu Qiaoyi, Yin Kun, Lin Fanghe, Zhang Yingkun, Song Jia, Ding Chenyu, Kang Dezhi, Yang Chaoyong
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, P. R. China.
Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350212, P. R. China.
Small Methods. 2025 Mar;9(3):e2401297. doi: 10.1002/smtd.202401297. Epub 2024 Oct 10.
Metabolic RNA labeling-based time-resolved single-cell RNA sequencing (scRNA-seq) has provided unprecedented tools to dissect the temporal dynamics and the complex gene regulatory networks of gene expression. However, this technology fails to reveal the spatial organization of cells in tissues, which also regulates the gene expression by intercellular communication. Herein, it is demonstrated that integrating time-resolved scRNA-seq with spatial transcriptomics is a new paradigm for spatiotemporal analysis. Metabolic RNA labeling-based time-resolved Well-TEMP-seq is first applied to profile the transcriptional dynamics of glioblastoma (GBM) cells and discover two potential pathways of EZH2-mediated mesenchymal transition in GBM. With spatial transcriptomics, it is further revealed that the crosstalk between CCL2 malignant cells and IL10 tumor-associated macrophages in the tumor microenvironment through an EZH2-FOSL2-CCL2 axis contributes to the mesenchymal transition in GBM. These discoveries show the power of integrative spatiotemporal scRNA-seq to elucidate the complex gene regulatory mechanism and advance the understanding of cellular processes in disease.
基于代谢RNA标记的时间分辨单细胞RNA测序（scRNA-seq）为剖析基因表达的时间动态和复杂基因调控网络提供了前所未有的工具。然而，这项技术无法揭示组织中细胞的空间组织，而细胞的空间组织也通过细胞间通讯来调节基因表达。在此证明，将时间分辨scRNA-seq与空间转录组学相结合是时空分析的一种新范式。基于代谢RNA标记的时间分辨Well-TEMP-seq首先应用于分析胶质母细胞瘤（GBM）细胞的转录动态，并发现GBM中EZH2介导的间充质转化的两条潜在途径。通过空间转录组学，进一步揭示了肿瘤微环境中CCL2恶性细胞与IL10肿瘤相关巨噬细胞之间通过EZH2-FOSL2-CCL2轴的相互作用促进了GBM的间充质转化。这些发现展示了整合时空scRNA-seq在阐明复杂基因调控机制和推进对疾病细胞过程理解方面的强大作用。
