Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease

Peter A. Szabo, Hanna Mendes Levitin, Michelle Miron, Mark E. Snyder, Takashi Senda, Jinzhou Yuan, Yim Ling Cheng, Erin C. Bush, Pranay Dogra, Puspa Thapa, Donna L. Farber, Peter A. Sims

Abstract

Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8+ T cells and an interferon-response state for CD4+ T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8+ compared to CD4+ T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.

Datasets

1. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease
Metadata
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Donor218066 cells
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Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease

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Source data

https://cellxgene.cziscience.com/collections/24d42e5e-ce6d-45ff-a66b-a3b3b715deaf

Alias names

E-HCAD-8, GSE126030, PMID31624246, PMC6797728

Cite this study

Szabo, P.A., Levitin, H.M., Miron, M., Snyder, M.E., Senda, T., Yuan, J., Cheng, Y.L., Bush, E.C., Dogra, P., Thapa, P. and Farber, D.L., 2019. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease. Nature communications, 10(1), p.4706. https://doi.org/10.1038/s41467-019-12464-3