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Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions

How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased...

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Autores principales: Gutierrez-Arcelus, Maria, Teslovich, Nikola, Mola, Alex R., Polidoro, Rafael B., Nathan, Aparna, Kim, Hyun, Hannes, Susan, Slowikowski, Kamil, Watts, Gerald F. M., Korsunsky, Ilya, Brenner, Michael B., Raychaudhuri, Soumya, Brennan, Patrick J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368609/
https://www.ncbi.nlm.nih.gov/pubmed/30737409
http://dx.doi.org/10.1038/s41467-019-08604-4
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author Gutierrez-Arcelus, Maria
Teslovich, Nikola
Mola, Alex R.
Polidoro, Rafael B.
Nathan, Aparna
Kim, Hyun
Hannes, Susan
Slowikowski, Kamil
Watts, Gerald F. M.
Korsunsky, Ilya
Brenner, Michael B.
Raychaudhuri, Soumya
Brennan, Patrick J.
author_facet Gutierrez-Arcelus, Maria
Teslovich, Nikola
Mola, Alex R.
Polidoro, Rafael B.
Nathan, Aparna
Kim, Hyun
Hannes, Susan
Slowikowski, Kamil
Watts, Gerald F. M.
Korsunsky, Ilya
Brenner, Michael B.
Raychaudhuri, Soumya
Brennan, Patrick J.
author_sort Gutierrez-Arcelus, Maria
collection PubMed
description How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function.
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spelling pubmed-63686092019-02-11 Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions Gutierrez-Arcelus, Maria Teslovich, Nikola Mola, Alex R. Polidoro, Rafael B. Nathan, Aparna Kim, Hyun Hannes, Susan Slowikowski, Kamil Watts, Gerald F. M. Korsunsky, Ilya Brenner, Michael B. Raychaudhuri, Soumya Brennan, Patrick J. Nat Commun Article How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function. Nature Publishing Group UK 2019-02-08 /pmc/articles/PMC6368609/ /pubmed/30737409 http://dx.doi.org/10.1038/s41467-019-08604-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gutierrez-Arcelus, Maria
Teslovich, Nikola
Mola, Alex R.
Polidoro, Rafael B.
Nathan, Aparna
Kim, Hyun
Hannes, Susan
Slowikowski, Kamil
Watts, Gerald F. M.
Korsunsky, Ilya
Brenner, Michael B.
Raychaudhuri, Soumya
Brennan, Patrick J.
Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
title Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
title_full Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
title_fullStr Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
title_full_unstemmed Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
title_short Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
title_sort lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368609/
https://www.ncbi.nlm.nih.gov/pubmed/30737409
http://dx.doi.org/10.1038/s41467-019-08604-4
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