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Quantifying cell fate change under different stochastic gene activation frameworks.

Xinxin Chen1, Ying Sheng1, Liang Chen1

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Summary
This summary is machine-generated.

Cell fate decisions depend on gene transcription levels. This study introduces a transcription threshold model, showing gene upregulation can suppress cell fate changes and noise can bidirectionally affect cell fate.

Keywords:
cell fate changemRNA distributionstatistical transcription thresholdstochastic gene transcriptiontranscription noise

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Area of Science:

  • * Molecular Biology
  • * Systems Biology
  • * Biophysics

Background:

  • * Gene transcription is inherently stochastic, leading to mRNA level fluctuations in identical cells.
  • * Understanding how transcriptional variability influences cell fate is crucial in single-cell biology.
  • * Previous models analyzed transcription dynamics, but extensions to complex gene activation frameworks were needed.

Purpose of the Study:

  • * To extend the mathematical framework for gene transcription probability (J_I) to more complex gene activation models.
  • * To investigate the impact of critical gene upregulation on cell fate determination.
  • * To analyze the dual role of transcription noise in modulating cell fate changes.

Main Methods:

  • * Developed and analyzed complex gene activation models beyond the classical telegraph model.
  • * Calculated the probability (J_I) of a cell reaching a specific transcription threshold (I).
  • * Validated model predictions using experimental data from bacterial, yeast, and mammalian cells.

Main Results:

  • * Critical gene upregulation was found to significantly suppress cell fate transitions.
  • * Transcription noise exhibits a bidirectional effect, either promoting or inhibiting cell fate changes.
  • * The transcription threshold (I) was successfully estimated from diverse cellular data.

Conclusions:

  • * The study provides a refined model for predicting cell fate commitment based on transcription dynamics.
  • * Findings suggest that high-dose HIV activators might suppress viral reactivation.
  • * Cells may dynamically adjust gene regulation noise based on environmental stress for survival.