Figure 9. Multi-state transcription dynamics achieve robust tissue level responses.
(A) Organised cell networks and gap junction cell-cell signalling in adult pituitary glands (lower panels), but not in immature pituitary glands (upper panels), leads to local correlation of transcription between cells. Across a large population of cells transcription dynamics are essentially random and uncoordinated. Multi-state transcription dynamics ('off', 'primed' and 'on' at various levels) contribute to transcriptional heterogeneity between cells as the time spent in each state is exponentially distributed. The schematic indicates putative regional signalling and signalling gradients across the pituitary, for example from hypothalamic dopamine (DA) and systemic estradiol (E2). Segments of pituitary tissue are represented with lactotroph cells (red) connected via gap junctions (black rectangles). Examples of single cell transcription profiles (left plots) and their relation to multi-state transcription dynamics (right plots), with 'off', 'primed' (dashed lines) and different levels of transcription in the 'on' state are shown. (B) Simulation of the telegraph model with priming demonstrates how decreasing the 'primed” period (at the dashed line) gives rise to a rapid robust response across a population of cells showing heterogeneous activity. The simulation was performed on fluorescence profiles from 100 cells, with the mean of these responses shown (black line) along with 5 representative cell responses (coloured lines).