Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells.
Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells.
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DOI：
10.3389/fimmu.2023.1108368
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发表时间：
2023
影响因子：
7.3
通讯作者：
Rothenberg, Ellen V. V.
中科院分区：
文献类型：
--
作者：
Shin, Boyoung;Rothenberg, Ellen V. V.
关键词：
T 细胞由多能祖细胞通过依赖胸腺内 Notch 信号传导并伴随广泛增殖的渐进过程发展而来。通过对分选群体的单细胞和批量 RNA 分析以及对前体-产物关系的直接测量，可以很好地表征导致 T 细胞谱系定型的阶段。这个过程不仅取决于Notch信号传导，还取决于多种转录因子，其中一些与干性和多能性相关，一些与替代谱系相关，还有一些与T细胞命运相关。这些因素在对立或半独立的 T 细胞基因调控网络 (GRN) 子电路中相互作用，这些子电路的定义越来越明确。该网络的新全面图景已经出现。重要的是，由于 GRN 中的关键因子在一个阶段可以与其他阶段明显不同的基因组位点结合，因此它们显着调节的基因也是阶段特异性的。对扰动的全局转录组分析揭示了 T 细胞承诺 GRN 的潜在模块化结构，将失去“干性”的决定与阻止替代命运的决定分开。最后，更新后的网络揭示了依赖于胸腺的 T 细胞程序与不依赖于胸腺的先天淋巴细胞 (ILC) 程序之间的密切关系。
T cells develop from multipotent progenitors by a gradual process dependent on intrathymic Notch signaling and coupled with extensive proliferation. The stages leading them to T-cell lineage commitment are well characterized by single-cell and bulk RNA analyses of sorted populations and by direct measurements of precursor-product relationships. This process depends not only on Notch signaling but also on multiple transcription factors, some associated with stemness and multipotency, some with alternative lineages, and others associated with T-cell fate. These factors interact in opposing or semi-independent T cell gene regulatory network (GRN) subcircuits that are increasingly well defined. A newly comprehensive picture of this network has emerged. Importantly, because key factors in the GRN can bind to markedly different genomic sites at one stage than they do at other stages, the genes they significantly regulate are also stage-specific. Global transcriptome analyses of perturbations have revealed an underlying modular structure to the T-cell commitment GRN, separating decisions to lose “stem-ness” from decisions to block alternative fates. Finally, the updated network sheds light on the intimate relationship between the T-cell program, which depends on the thymus, and the innate lymphoid cell (ILC) program, which does not.
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影响因子：
8
作者：
Cante-Barrett, Kirsten;Meijer, Mariska T.;Cordo, Valentina;Hagelaar, Rico;Yang, Wentao;Yu, Jiyang;Smits, Willem K.;Nulle, Marloes E.;Jansen, Joris P.;Pieters, Rob;Yang, Jun J.;Haigh, Jody J.;Goossens, Steven;Meijerink, Jules P. P.
通讯作者：
Meijerink, Jules P. P.
影响因子：
10.5
作者：
Champhekar A;Damle SS;Freedman G;Carotta S;Nutt SL;Rothenberg EV
通讯作者：
Rothenberg EV
影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
影响因子：
20.3
作者：
Cai, Mi;Langer, Ellen M.;Murphy, Kenneth M.
通讯作者：
Murphy, Kenneth M.
影响因子：
30.5
作者：
Chen, Edward L. Y.;Thompson, Patrycja K.;Zuniga-Pflucker, Juan Carlos
通讯作者：
Zuniga-Pflucker, Juan Carlos