Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes

Serena Meraviglia, Gabriele Pizzolato, Francesco Dieli, Don-Marc Franchini, Marie Tosolini, Carine Valle, Mary Poupot, Camille Laurent, Pierre Milpied, Hannah Kaminski, Fréderic Martins, Anne Quillet-Mary, Sarah Cadot, Gabriele Pizzolato, Julie Déchanet-Merville, Fréderic Martins, Julie Déchanet-Merville, Loic Ysebaert, Fréderic Pont, Pierre MervilleJean-Jacques Fournié, Delphine Labourdette

Risultato della ricerca: Articlepeer review

24 Citazioni (Scopus)

Abstract

γδ T lymphocytes represent ∼1% of human peripheral blood mononuclear cells and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current single-cell RNA sequencing (scRNA-seq) studies do not identify γδ T lymphocytes because their transcriptomes at the single-cell level are unknown. Here we show that high-resolution clustering of large scRNA-seq datasets and a combination of gene signatures allow the specific detection of human γδ T lymphocytes and identification of their T cell receptor (TCR)Vδ1 and TCRVδ2 subsets in large datasets from complex cell mixtures. In t-distributed stochastic neighbor embedding plots from blood and tumor samples, the few γδ T lymphocytes appear collectively embedded between cytotoxic CD8 T and NK cells. Their TCRVδ1 and TCRVδ2 subsets form close yet distinct subclusters, respectively neighboring NK and CD8 T cells because of expression of shared and distinct cytotoxic maturation genes. Similar pseudotime maturation trajectories of TCRVδ1 and TCRVδ2 γδ T lymphocytes were discovered, unveiling in both subsets an unattended pool of terminally differentiated effector memory cells with preserved proliferative capacity, a finding confirmed by in vitro proliferation assays. Overall, the single-cell transcriptomes of thousands of individual γδ T lymphocytes from different CMV+ and CMV- donors reflect cytotoxic maturation stages driven by the immunological history of donors. This landmark study establishes the rationale for identification, subtyping, and deep characterization of human γδ T lymphocytes in further scRNA-seq studies of complex tissues in physiological and disease conditions.
Lingua originaleEnglish
pagine (da-a)11906-11915
Numero di pagine10
RivistaProceedings of the National Academy of Sciences of the United States of America
Volume116
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

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