Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling

Yanchuan Li, Huamei Li, Cheng Peng, Ge Meng, Yijun Lu, Honglin Liu, Li Cui, Huan Zhou, Zhu Xu, Lingyun Sun, Lihong Liu (), Qing Xiong (), Beicheng Sun () and Shiping Jiao ()
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Yanchuan Li: Nanjing Medical University
Huamei Li: the Affiliated Hospital of Nanjing University Medical School
Cheng Peng: the Affiliated Hospital of Nanjing University Medical School
Ge Meng: Zhejiang University
Yijun Lu: First Affiliated Hospital of Anhui Medical University
Honglin Liu: China-Japan Friendship Hospital
Li Cui: Southern Medical University
Huan Zhou: The First Affiliated Hospital of Bengbu Medical College
Zhu Xu: First Affiliated Hospital of Anhui Medical University
Lingyun Sun: the Affiliated Hospital of Nanjing University Medical School
Lihong Liu: China-Japan Friendship Hospital
Qing Xiong: the Affiliated Hospital of Nanjing University Medical School
Beicheng Sun: First Affiliated Hospital of Anhui Medical University
Shiping Jiao: Zhejiang University

Nature Communications, 2024, vol. 15, issue 1, 1-25

Abstract: Abstract The structural components of the thymus are essential for guiding T cell development, but a thorough spatial view is still absent. Here we develop the TSO-his tool, designed to integrate multimodal data from single-cell and spatial transcriptomics to decipher the intricate structure of human thymus. Specifically, we characterize dynamic changes in cell types and critical markers, identifying ELOVL4 as a mediator of CD4+ T cell positive selection in the cortex. Utilizing the mapping function of TSO-his, we reconstruct thymic spatial architecture at single-cell resolution and recapitulates classical cell types and their essential co-localization for T cell development; additionally, previously unknown co-localization relationships such as that of CD8αα with memory B cells and monocytes are identified. Incorporating VDJ sequencing data, we also delineate distinct intermediate thymocyte states during αβ T cell development. Overall, these insights enhance our understanding of thymic biology and may inform therapeutic interventions targeting T cell-mediated immune responses.

Date: 2024
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DOI: 10.1038/s41467-024-51767-y

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