title: Spatially coordinated dynamic gene transcription in living pituitary tissue.
abstract: 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.
authors.affiliation: Centre for Endocrinology and Diabetes, University of Manchester, Manchester, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Featherstone
authors.affiliation: Department of Statistics, University of Warwick, Coventry, United Kingdom.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Hey
authors.affiliation: Warwick Systems Biology, University of Warwick, Coventry, United Kingdom.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Momiji
authors.affiliation: Systems Biology Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Anne V
authors.initials: AV
authors.lastname: McNamara
authors.affiliation: Centre for Endocrinology and Diabetes, University of Manchester, Manchester, United Kingdom.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Patist
authors.affiliation: Centre for Endocrinology and Diabetes, University of Manchester, Manchester, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Woodburn
authors.affiliation: Systems Biology Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: David G
authors.initials: DG
authors.lastname: Spiller
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Christian
authors.affiliation: MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alan S
authors.initials: AS
authors.lastname: McNeilly
authors.affiliation: The Molecular Physiology Group, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mullins
authors.affiliation: Department of Statistics, University of Warwick, Coventry, United Kingdom.
authors.forename: Bärbel F
authors.initials: BF
authors.lastname: Finkenstädt
authors.affiliation: Warwick Systems Biology, University of Warwick, Coventry, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Rand
authors.affiliation: Systems Biology Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Michael R H
authors.initials: MR
authors.lastname: White
authors.affiliation: Centre for Endocrinology and Diabetes, University of Manchester, Manchester, United Kingdom.
authors.forename: Julian R E
authors.initials: JR
authors.lastname: Davis
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D061848:Optical Imaging; D010902:Pituitary Gland / Q000502:physiology*; D011916:Rats, Inbred F344; D062211:Spatio-Temporal Analysis; D014158:Transcription, Genetic
keywords: Live-Cell Microscopy; Pituitary; Spatial Organisation; Stochastic Modelling; Transcription Dynamics; cell biology; computational biology; rat; systems biology
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