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
- Peter A Szabo: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA. ORCID
- Hanna Mendes Levitin: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
- Michelle Miron: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
- Mark E Snyder: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
- Takashi Senda: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
- Jinzhou Yuan: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
- Yim Ling Cheng: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
- Erin C Bush: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
- Pranay Dogra: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
- Puspa Thapa: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.
- Donna L Farber: Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA. df2396@cumc.columbia.edu. ORCID
- Peter A Sims: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA. pas2182@cumc.columbia.edu. ORCID
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.
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
