A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation.
A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation.
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DOI：
10.1016/j.immuni.2018.04.015
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发表时间：
2018-06-19
期刊：
影响因子：
32.4
通讯作者：
Maehr R
中科院分区：
文献类型：
--
作者：
Kernfeld EM;Genga RMJ;Neherin K;Magaletta ME;Xu P;Maehr R
胸腺发育对于适应性免疫系统是至关重要的，然而仍然需要在单细胞分辨率下捕获胸腺器官发生的全面转录框架。我们应用单细胞RNA-seq捕获了胸腺发育的8天，T细胞受体重排的扰动和体外器官培养，产生了24，279个细胞的概况。我们解决了发展中的淋巴细胞的转录异质性，和遗传扰动证实了常规和非常规淋巴细胞的T细胞的身份。我们的特点是胸腺上皮细胞在体内的成熟动力学，分类细胞成熟状态的胸腺器官培养，并揭示了胸腺上皮细胞的内在能力，以保持转录的规律性，尽管暴露于外源性视黄酸。最后，通过整合人类GWAS数据和自身免疫性疾病相关基因的细胞图谱，我们暗示胚胎胸腺驻留细胞可能参与自身免疫性疾病的病因。这一资源为胸腺器官发生的生物学发现和分子分析提供了单细胞转录框架。
Thymus development is critical to the adaptive immune system, yet a comprehensive transcriptional framework capturing thymus organogenesis at single cell resolution is still needed. We applied single-cell RNA-seq to capture eight days of thymus development, perturbations of T-cell receptor rearrangement, and in vitro organ cultures, producing profiles of 24,279 cells. We resolved transcriptional heterogeneity of developing lymphocytes, and genetic perturbation confirmed T cell identity of conventional and non-conventional lymphocytes. We characterized maturation dynamics of thymic epithelial cells in vivo, classified cell maturation state in a thymic organ culture, and revealed the intrinsic capacity of thymic epithelium to preserve transcriptional regularity despite exposure to exogenous retinoic acid. Finally, by integrating the cell atlas with human GWAS data and autoimmune disease-related genes, we implicated embryonic thymus resident cells as possible participants in autoimmune disease etiologies. This resource provides a single-cell transcriptional framework for biological discovery and molecular analysis of thymus organogenesis.
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DOI：
10.1084/jem.20151780
发表时间：
2016-07-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Akiyama N;Takizawa N;Miyauchi M;Yanai H;Tateishi R;Shinzawa M;Yoshinaga R;Kurihara M;Demizu Y;Yasuda H;Yagi S;Wu G;Matsumoto M;Sakamoto R;Yoshida N;Penninger JM;Kobayashi Y;Inoue J;Akiyama T
通讯作者：
Akiyama T
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
30.5
作者：
Brennecke P;Reyes A;Pinto S;Rattay K;Nguyen M;Küchler R;Huber W;Kyewski B;Steinmetz LM
通讯作者：
Steinmetz LM
DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
影响因子：
30.5
作者：
Ishizuka IE;Chea S;Gudjonson H;Constantinides MG;Dinner AR;Bendelac A;Golub R
通讯作者：
Golub R