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Collective signalling drives rapid jumping between cell states.

Elizabeth R Westbrook1, Tchern Lenn1, Jonathan R Chubb1

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Summary
This summary is machine-generated.

Cell development involves rapid gene expression changes, but regulation in complex populations is unclear. This study reveals cyclic adenosine monophosphate (cAMP) signaling drives these transitions in Dictyostelium, impacting cell state changes.

Keywords:
In vivo imagingCell state transitionCollective behaviourExcitable signallingMS2 imagingOptogeneticsOscillationPositive feedbackStem cell nicheTranscriptional noise

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Area of Science:

  • Cellular and Molecular Biology
  • Developmental Biology
  • Systems Biology

Background:

  • Cellular development can occur in abrupt transitions, characterized by widespread gene expression changes.
  • Understanding the regulation of these rapid cell state transitions in complex cellular populations receiving multiple signals remains a challenge.

Purpose of the Study:

  • To investigate the regulatory mechanisms governing rapid cell state transitions during development in Dictyostelium.
  • To elucidate the role of cyclic adenosine monophosphate (cAMP) signaling in coordinating gene expression changes during development.

Main Methods:

  • Utilized continuous single-cell transcriptomics to analyze gene expression dynamics over time.
  • Employed simultaneous imaging of transcription and signaling pathways.
  • Used optogenetics to control cAMP signaling pulses and assess gene responses.

Main Results:

  • Identified a distinct 'jump' in global gene expression marking different cell states.
  • Demonstrated this gene expression jump coincides with the onset of collective cAMP oscillations.
  • Showed that specific genes respond to distinct features of cAMP signaling dynamics, with late genes heavily dependent on cAMP and early genes requiring additional input.

Conclusions:

  • The coupling of collective signaling, specifically cAMP oscillations, with gene expression provides a robust mechanism for cell state transitions in complex environments.
  • Sharp gene expression transitions alone may not be sufficient for developmental commitment.