Pulsatile patterns of pituitary hormone gene expression change during development

Abstract

Important questions in biology have emerged recently concerning the timing of transcription in living cells. Studies on clonal cell lines have shown that transcription is often pulsatile and stochastic, with implications for cellular differentiation. Currently, information regarding transcriptional activity at cellular resolution within a physiological context remains limited. To investigate single-cell transcriptional activity in real-time in living tissue we used bioluminescence imaging of pituitary tissue from transgenic rats in which luciferase gene expression is driven by a pituitary hormone gene promoter. We studied fetal and neonatal pituitary tissue to assess whether dynamic patterns of transcription change during tissue development. We show that gene expression in single cells is highly pulsatile at the time endocrine cells first appear but becomes stabilised as the tissue develops in early neonatal life. This stabilised transcription pattern might depend upon tissue architecture or paracrine signalling, as isolated cells, generated from enzymatic dispersion of the tissue, display pulsatile luminescence. Nascent cells in embryonic tissue also showed coordinated transcription activity over short distances further indicating that cellular context is important for transcription activity. Overall, our data show that cells alter their patterns of gene expression according to their context and developmental stage, with important implications for cellular differentiation.

Plasticity of the Prolactin (PRL) Axis: Mechanisms Underlying Regulation of Output in Female Mice

“…Indeed, PRL gene transcription is coordinated at the population level, a trait which is lost when cells are dispersed and cultured in two-dimensions [101,102]. Likewise, lactotroph transcription is pulsatile during embryogenesis before stabilising in the postnatal period [103]; it is tempting to speculate that this transition may coincide with the final specification, maturation and placement of the PRL-network. However, whether cycles in lactotroph transcription are the cause or consequence of PRL-network development remains unknown.…”

How can a binary switch within the pars tuberalis control seasonal timing of reproduction?

“…Prolactin expression follows a binary 'on-off' process, with activity of individual cells being unpredictable, but the overall activity of a group of cells being predictable (Hey et al 2015, Featherstone et al 2016. The conclusions from these study were that heterogeneous single-cell responses allowed the tissue to be more functionally adaptive to the environment and result in more robust tissue-level responses, avoiding inappropriate amplification of signals through feedback mechanisms (Featherstone et al 2011, Hey et al 2015.…”

“…However, stochastic heterogeneity in single-cell response can lead to tissue progressive responses. Release of prolactin from the pituitary, for example, is based on heterogeneous patterns of gene expression at a single-cell level but a wellregulated average level of gene expression is maintained (Featherstone et al 2011. Prolactin expression follows a binary 'on-off' process, with activity of individual cells being unpredictable, but the overall activity of a group of cells being predictable (Hey et al 2015, Featherstone et al 2016.…”

Le rôle des phénomènes aléatoires dans le cancer

“…Ces données nous permettent de renouveler notre vision de l'origine et du rôle des cellules souches cancéreuses. Il faut d'abord relever que si les cellules souches embryonnaires expriment leur génome de manière très aléatoire et généralisée in vitro [14] comme in vivo [22], la structuration tissulaire est au contraire marquée par une diminution de la stochasticité de l'expression des gènes [23,24]. La pluripotence des cellules souches serait le fruit d'un état d'instabilité intrinsèque de l'expression des gènes, responsable lui-même du grand nombre de voies développementales possibles pour ces cellules.…”