Integrating Metabolic RNA Labeling-Based Time-Resolved Single-Cell RNA Sequencing with Spatial Transcriptomics for Spatiotemporal Transcriptomic Analysis

Xiaoyong Chen; Shichao Lin; Honghai You; Jinyuan Chen; Qiaoyi Wu; Kun Yin; Fanghe Lin; Yingkun Zhang; Jia Song; Chenyu Ding; Dezhi Kang; Chaoyong Yang

doi:10.1002/smtd.202401297

Integrating Metabolic RNA Labeling-Based Time-Resolved Single-Cell RNA Sequencing with Spatial Transcriptomics for Spatiotemporal Transcriptomic Analysis

Small Methods. 2024 Oct 10:e2401297. doi: 10.1002/smtd.202401297. Online ahead of print.

Authors

Xiaoyong Chen^{1

2}, Shichao Lin³, Honghai You^{1

2}, Jinyuan Chen⁴, Qiaoyi Wu⁵, Kun Yin³, Fanghe Lin³, Yingkun Zhang³, Jia Song⁶, Chenyu Ding^{1

2}, Dezhi Kang^{1

2}, Chaoyong Yang^{3

6}

Affiliations

¹ Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, P. R. China.
² Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350212, P. R. China.
³ State Key Laboratory of Physical Chemistry of Solid Surfaces, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, P. R. China.
⁴ Department of Ophthalmology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, P. R. China.
⁵ Department of Trauma Center & Emergency Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, P. R. China.
⁶ Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200120, P. R. China.

PMID: 39390840
DOI: 10.1002/smtd.202401297

Abstract

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.

Keywords: EZH2; glioblastoma; mesenchymal transition; single‐cell; spatiotemporal.

Abstract

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