淋巴细胞的先天状态由转录状态定义，反映了增殖和效应功能之间的平衡。
Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions.
机构信息
Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, 02115.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, 02142, USA.
出版信息
Nat Commun. 2019 Feb 8;10(1):687. doi: 10.1038/s41467-019-08604-4.
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.
先天 T 细胞（ITC），包括不变自然杀伤 T（iNKT）细胞、黏膜相关不变 T（MAIT）细胞和 γδ T 细胞，如何维持平衡的效应状态一直不清楚。在这里，我们使用低投入和单细胞 RNA-seq 技术对人类淋巴细胞群进行了研究。无偏倚的转录组分析揭示了一个连续的“先天梯度”，一端是适应性 T 细胞，另一端依次是 MAIT、iNKT、γδ T 和自然杀伤细胞。单细胞 RNA-seq 揭示了四种广泛的先天状态，以及经典先天和适应性群体中的异质性。转录组和功能数据表明，先天状态的特征是预先形成的 mRNA 编码效应功能，但增殖受损，核糖体基因的基础表达降低。总之，我们的数据为 ITC 的平衡状态提供了新的见解，其中先天状态是由转录协调的快速细胞生长和快速效应功能之间的权衡决定的。
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