Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice
Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice
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DOI：
10.1038/s42003-019-0688-8
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发表时间：
2019-11-29
影响因子：
5.9
通讯作者：
Kobayashi, Tetsuya J.
中科院分区：
文献类型：
--
作者：
Kaneko, Kazumasa B.;Tateishi, Ryosuke;Kobayashi, Tetsuya J.
胸腺串扰是胸腺细胞和胸腺环境之间的一组相互调节，与协调适当的胸腺细胞发育以及胸腺从各种外源性损伤中恢复有关。在这项工作中，相互作用塑造胸腺串扰和由此产生的动态胸腺细胞和胸腺上皮细胞推断辐射诱导的恢复动力学的定量分析和建模的基础上。该分析确定了与已知分子证据一致的调节相互作用，并揭示了它们在恢复过程中的动态作用。此外，该分析还预测，随后的实验验证，以前未认识到的调节CD4+CD8+双阳性胸腺细胞，暂时增加其增殖率后，在其人口规模的减少。我们的模型建立了一个关键的一步，对动态的理解胸腺串扰作为一个监管网络系统。
Thymic crosstalk, a set of reciprocal regulations between thymocytes and the thymic environment, is relevant for orchestrating appropriate thymocyte development as well as thymic recovery from various exogenous insults. In this work, interactions shaping thymic crosstalk and the resultant dynamics of thymocytes and thymic epithelial cells are inferred based on quantitative analysis and modeling of the recovery dynamics induced by irradiation. The analysis identifies regulatory interactions consistent with known molecular evidence and reveals their dynamic roles in the recovery process. Moreover, the analysis also predicts, and a subsequent experiment verifies, a previously unrecognized regulation of CD4+CD8+ double positive thymocytes which temporarily increases their proliferation rate upon the decrease in their population size. Our model establishes a pivotal step towards the dynamic understanding of thymic crosstalk as a regulatory network system.