eLife · 2016 · 60 citations · 45 references
Life SciencesCell BiologyMolecular BiologyGene ExpressionTranscriptional RegulationTranscriptomicsCell-state HeterogeneityGene Expression DynamicsGene Expression ImagingSingle-cell TranscriptomicsSpatial Gene ExpressionTemporal TranscriptomicsLive-cell ImagingPituitary PhysiologyProlactin Gene ExpressionSingle-cell Temporal TranscriptomicsSingle-cell Transcription DynamicsSpatiotemporal Expression DynamicsTemporal Gene Expression DynamicsTranscriptional Dynamics
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.
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