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Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling
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Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling
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Journal Article
Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling
2024
Overview
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.
Thymus is important for shaping T cell immunity, but spatial insights at cellular and molecular level are still scarce. Here the author use multi-omics approaches and custom algorithms to reconstruct the spatial organization of human thymi for both confirming known features and unrevealing new components during thymocyte maturation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/91
/ 82/1
/ 82/51
/ 82/80
/ CD4-Positive T-Lymphocytes - metabolism
/ Gene Expression Profiling - methods
/ Humanities and Social Sciences
/ Humans
/ Immune response (cell-mediated)
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Science
/ Single-Cell Analysis - methods
/ Thymus
