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Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
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Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation

Soroush Tahmasebi1,2, Seyed Mehdi Jafarnejad1,2, Ingrid S Tam1,2

  • 1Goodman Cancer Research Center, McGill University, Montreal, QC H3A 1A3, Canada.

Proceedings of the National Academy of Sciences of the United States of America
|November 3, 2016
PubMed

Insights

Yin-yang 2 (YY2) controls mouse embryonic stem cell (mESC) self-renewal and differentiation. Its expression is regulated by translation inhibitors (4E-BPs) and splicing factor PTBP1, impacting pluripotency factors like Oct4.

Area of Science:

  • Developmental Biology
  • Gene Regulation
  • Stem Cell Biology

Background:

  • Translational control is crucial for early embryonic development.
  • Mouse embryonic stem cells (mESCs) rely on precise gene expression for self-renewal and differentiation.
  • Eukaryotic initiation factor 4E-binding proteins (4E-BPs) are key regulators of translation.

Purpose of the Study:

  • To identify and characterize novel regulators of mESC self-renewal and differentiation.
  • To elucidate the regulatory mechanisms controlling the expression of key pluripotency factors.
  • To investigate the role of translational control in mESC lineage commitment.

Main Methods:

  • Identification of Yin-yang 2 (YY2) as a transcriptional regulator in mESCs.
  • Analysis of YY2's regulation by 4E-BPs.
  • Investigation of YY2's role in controlling pluripotency factors (Oct4, Esrrb).
  • Assessment of YY2's effect on mESC differentiation into cardiovascular lineages.
  • Characterization of the role of Polypyrimidine tract-binding protein 1 (PTBP1) in Yy2 mRNA processing.

Main Results:

  • YY2 is a critical regulator of mESC self-renewal and pluripotency.
  • YY2 controls the expression of key pluripotency factors Oct4 and Esrrb.
  • Overexpression of YY2 induces differentiation of mESCs into cardiovascular lineages.
  • PTBP1-mediated intron retention in Yy2 mRNA confers 4E-BP-dependent translational suppression.
  • A multilayered regulatory mechanism controls YY2 expression.

Conclusions:

  • YY2 is a significant regulator of mESC self-renewal and lineage commitment.
  • A novel regulatory pathway involving 4E-BPs, PTBP1, and Yy2 mRNA splicing controls YY2 expression.
  • This study reveals a complex mechanism governing stem cell fate decisions through translational control.
Keywords:
4E-BPsPTBPYY2embryonic stem cellmRNA translation

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