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Nature communications
10 17, 2019;10 (1): 4706.

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
Author Information
  1. Peter A Szabo: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA. ORCID
  2. Hanna Mendes Levitin: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
  3. Michelle Miron: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  4. Mark E Snyder: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  5. Takashi Senda: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  6. Jinzhou Yuan: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
  7. Yim Ling Cheng: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
  8. Erin C Bush: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
  9. Pranay Dogra: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  10. Puspa Thapa: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  11. Donna L Farber: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA. df2396@cumc.columbia.edu. ORCID
  12. Peter A Sims: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA. pas2182@cumc.columbia.edu. ORCID
PMID: 31624246 DOI: 10.1038/s41467-019-12464-3

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.

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Grants

  1. P01 AI106697/NIAID NIH HHS
  2. T32 AI106711/NIAID NIH HHS
  3. T32 GM008224/NIGMS NIH HHS
  4. U19 AI128949/NIAID NIH HHS

MeSH Term

CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cells, Cultured
Humans
Lung
Lymph Nodes
Lymphocyte Activation
Mucous Membrane
Neoplasms
Single-Cell Analysis
T-Lymphocytes
Transcriptome
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000111 (A single cell reference map for human blood and tissue T cell activation)

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