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

Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; Déchanet-Merville, J.; Fournié, J.

Risultato della ricerca: Article

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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)201818488-
Numero di pagine0
RivistaProceedings of the National Academy of Sciences of the United States of America
Stato di pubblicazionePublished - 2019

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Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; Déchanet-Merville, J.; Fournié, J. (2019). Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America, 201818488-.

Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes. / Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; Déchanet-Merville, J.; Fournié, J.

In: Proceedings of the National Academy of Sciences of the United States of America, 2019, pag. 201818488-.

Risultato della ricerca: Article

Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; Déchanet-Merville, J.; Fournié, J. 2019, 'Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes', Proceedings of the National Academy of Sciences of the United States of America, pagg. 201818488-.
Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; Déchanet-Merville, J.; Fournié, J. Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America. 2019;201818488-.
Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; Déchanet-Merville, J.; Fournié, J. / Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; pagg. 201818488-.
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title = "Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes",
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.",
author = "{Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; D{\'e}chanet-Merville, J.; Fourni{\'e}, J.} and Francesco Dieli and Serena Meraviglia and Gabriele Pizzolato",
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T1 - Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes

AU - Kaminski, H.; Tosolini, M.; Franchini, D.; Pont, F.; Martins, F.; Valle, C.; Labourdette, D.; Cadot, S.; Quillet-Mary, A.; Poupot, M.; Laurent, C.; Ysebaert, L.; Merville, P.; Milpied, P.; Déchanet-Merville, J.; Fournié, J.

AU - Dieli, Francesco

AU - Meraviglia, Serena

AU - Pizzolato, Gabriele

PY - 2019

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N2 - 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.

AB - 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.

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M3 - Article

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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