Spatially coordinated dynamic gene transcription in living pituitary tissue

Spatially coordinated dynamic gene transcription in living pituitary tissue
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DOI:
10.7554/elife.08494
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发表时间:
2016-02-01
期刊:
影响因子:
7.7
通讯作者:
Davis, Julian R. E.
Davis, Julian R. E.
中科院分区:
生物学1区
文献类型:
--
作者:
Featherstone, Karen;Hey, Kirsty;Davis, Julian R. E.

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单细胞中单个基因的转录通常是脉动的和随机的。一个关键问题是这种行为如何影响组织表型,但随着时间的推移,在活细胞中定量分析这一点一直是一个挑战,而不是研究基因表达状态的快照。我们已经使用报告基因表达的成像来跟踪活垂体组织中的转录。我们将活细胞成像数据与统计建模相结合,用于定量实时估计整个组织中转录状态之间切换的时间。多个水平的转录速率被确定,表明基因表达不是一个简单的二元“开-关”过程。未成熟的组织表现出较短的持续时间的高表达状态比成人。在成人垂体组织中,直接细胞接触,包括缝隙连接允许催乳素基因表达的局部空间协调。我们的研究结果确定了单细胞的异质性转录动力学如何有助于整体组织行为。
Transcription at individual genes in single cells is often pulsatile and stochastic. A key question emerges regarding how this behaviour contributes to tissue phenotype, but it has been a challenge to quantitatively analyse this in living cells over time, as opposed to studying snap-shots of gene expression state. We have used imaging of reporter gene expression to track transcription in living pituitary tissue. We integrated live-cell imaging data with statistical modelling for quantitative real-time estimation of the timing of switching between transcriptional states across a whole tissue. Multiple levels of transcription rate were identified, indicating that gene expression is not a simple binary 'on-off' process. Immature tissue displayed shorter durations of high-expressing states than the adult. In adult pituitary tissue, direct cell contacts involving gap junctions allowed local spatial coordination of prolactin gene expression. Our findings identify how heterogeneous transcriptional dynamics of single cells may contribute to overall tissue behaviour.