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Transcriptome-wide variability in single embryonic development cells.

Vincent Piras1, Masaru Tomita1, Kumar Selvarajoo1

  • 11] Institute for Advanced Biosciences, Keio University, 14-1 Baba-cho, 997-0035, Tsuruoka, Japan [2] Systems Biology Program, Graduate School of Media and Governance, Keio University, 5322 Endo, 252-0882, Fujisawa, Japan.

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Early embryonic development shows a shift in molecular variability. Transcriptome-wide gene expression becomes highly diverse and variable from the 8-cell stage due to transcriptional regulation.

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Area of Science:

  • Developmental Biology
  • Genomics
  • Molecular Biology

Background:

  • Molecular heterogeneity within single cells is vital for cell fate diversification.
  • The impact of molecular variability on embryonic development remains largely unexplored.

Purpose of the Study:

  • To investigate the origins of transcriptome-wide variability during human and mouse embryonic development, from oocytes to blastocysts.
  • To understand the transition in gene expression diversity and variability throughout early development.

Main Methods:

  • Analysis of RNA-Seq datasets from human and mouse embryos.
  • Evaluation of Pearson correlation, Shannon entropy, and noise patterns (η(2) vs. μ).
  • Utilisation of a stochastic transcriptional model to simulate gene expression patterns.

Main Results:

  • A phase transition was observed, moving from low to saturating levels of transcriptome-wide expression diversity and variability.
  • Transcriptome-wide regulation initiates around the 2-cell stage.
  • Significant variability emerges from the 8-cell stage, driven by amplification and quantal transcriptional activity.

Conclusions:

  • Early embryonic development exhibits a distinct shift in molecular variability.
  • Stochastic transcriptional modeling supports the observed patterns of gene expression dynamics.
  • The 8-cell stage is a critical period for the emergence of significant transcriptome-wide variability.