Disentangling juxtacrine from paracrine signalling in dynamic tissue

Area of Science:

• Molecular Endocrinology
• Systems Biology
• Cellular Communication

Background:

• Prolactin, a key pituitary hormone, has poorly understood cell-level production mechanisms.
• Previous studies revealed dynamic, stochastic prolactin gene transcription with space-time coordination.
• The specific intercellular communication mediating this organization remained unidentified.

Purpose of the Study:

• To identify the type of intercellular communication coordinating prolactin gene transcription.
• To distinguish between juxtacrine and paracrine signaling in pituitary tissue.
• To determine if coordination affects transcriptional or post-transcriptional activities.

Main Methods:

• Development of a statistical model analyzing expression time series similarity using Euclidean and geodesic distances.
• Application of stochastic switch modeling to infer cellular transcriptional profiles.
• Computational modeling of inter-cell juxtacrine coupling to simulate gene expression dynamics.

Main Results:

• Analysis indicated a dominance of juxtacrine signaling over paracrine signaling.
• Spatial cellular coordination was found to involve transcription coupling via juxtacrine signaling.
• Computational model simulations successfully replicated observed space-time transcriptional coordination.

Conclusions:

• Juxtacrine signaling is the primary mechanism for space-time organization in prolactin gene transcription.
• The observed coordination is at the transcriptional level, mediated by cell-to-cell contact.
• The developed computational model serves as a prototype for studying tissue-level gene expression.