High Dimensional Single-Cell Analysis Reveals iNKT Cell Developmental Trajectories and Effector Fate Decision
High Dimensional Single-Cell Analysis Reveals iNKT Cell Developmental Trajectories and Effector Fate Decision
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DOI：
10.1016/j.celrep.2020.108116
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发表时间：
2020-09-08
期刊：
影响因子：
8.8
通讯作者：
Paget, Christophe
中科院分区：
文献类型：
--
作者：
Baranek, Thomas;Lebrigand, Kevin;Paget, Christophe
CD 1d限制性不变自然杀伤T（iNKT）细胞是一类独特的T淋巴细胞，具有强大的调节和效应免疫功能。虽然这些功能是在胸腺个体发育过程中获得的，但产生离散效应子亚群的事件序列仍不清楚。使用无偏的单细胞转录组学分析结合功能测定，我们揭示了胸腺iNKT细胞，特别是iNKT 1细胞之间的未被赞赏的多样性。数学建模和生物学方法揭示了一个发育图，其中iNKT 2细胞构成了iNKT 1和iNKT 17细胞生成的瞬时分支点，这调和了先前提出的两个模型。此外，我们确定转录辅因子Four-and-a-half LIM结构域蛋白2（FHL 2）作为iNKT 1特化的关键细胞内在调节因子。因此，这些数据说明了引导iNKT细胞效应子命运的不断变化的转录网络。
CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that gives rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomic analysis combined with functional assays, we reveal an unappreciated diversity among thymic iNKT cells, especially among iNKT1 cells. Mathematical modeling and biological methods unravel a developmental map whereby iNKT2 cells constitute a transient branching point toward the generation of iNKT1 and iNKT17 cells, which reconciles the two previously proposed models. In addition, we identify the transcription co-factor Four-and-a-half LIM domains protein 2 (FHL2) as a critical cell-intrinsic regulator of iNKT1 specification. Thus, these data illustrate the changing transcriptional network that guides iNKT cell effector fate.