A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation.
A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation.
复制标题
在胸腺细胞分化过程中，基因组宽的转录模型是对TCR前信号传导的复杂响应。
DOI：
10.18632/oncotarget.5796
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发表时间：
2015-10-06
期刊：
影响因子：
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通讯作者：
Crompton T
中科院分区：
文献类型：
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作者：
Sahni H;Ross S;Barbarulo A;Solanki A;Lau CI;Furmanski A;Saldaña JI;Ono M;Hubank M;Barenco M;Crompton T
发育中的胸腺细胞需要tcr前信号才能从CD4 - CD8 -双阴性细胞分化为CD4+CD8+双阳性细胞。在这里，我们跟踪了同步分化双阴性胸腺细胞群体对前tcr信号的转录反应。这个时间序列分析揭示了一个复杂的转录反应，在检测到细胞表面表型变化之前，数千个基因被上调和下调。对单个基因的RNA降解的全基因组测量显示，不同基因之间的降解速率存在很大的异质性。因此，我们使用时间过程表达和降解数据以及全基因组转录建模（GWTM）策略来模拟tcr前信号转导上调基因的转录反应。该分析揭示了五种主要的时间上不同的转录活动，它们随着时间的推移上调转录，而下调表达则发生在三个波中。因此，我们的模型将已知的调节因子置于时间角度，并确定了胸腺细胞分化的新候选调节因子。
Developing thymocytes require pre-TCR signalling to differentiate from CD4−CD8− double negative to CD4+CD8+ double positive cell. Here we followed the transcriptional response to pre-TCR signalling in a synchronised population of differentiating double negative thymocytes. This time series analysis revealed a complex transcriptional response, in which thousands of genes were up and down-regulated before changes in cell surface phenotype were detected. Genome-wide measurement of RNA degradation of individual genes showed great heterogeneity in the rate of degradation between different genes. We therefore used time course expression and degradation data and a genome wide transcriptional modelling (GWTM) strategy to model the transcriptional response of genes up-regulated on pre-TCR signal transduction. This analysis revealed five major temporally distinct transcriptional activities that up regulate transcription through time, whereas down-regulation of expression occurred in three waves. Our model thus placed known regulators in a temporal perspective, and in addition identified novel candidate regulators of thymocyte differentiation.