Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 02 2019
08 02 2019
Historique:
received:
27
03
2018
accepted:
21
01
2019
entrez:
10
2
2019
pubmed:
10
2
2019
medline:
9
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30737409
doi: 10.1038/s41467-019-08604-4
pii: 10.1038/s41467-019-08604-4
pmc: PMC6368609
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
687Subventions
Organisme : NIAID NIH HHS
ID : R01 AI113046
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR063759
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009379
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI063428
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI111224
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR007530
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM092691
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI063428
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI102945
Pays : United States
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