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Epithelial-Mesenchymal Transition Functions as a Driver for the Direct Conversion of Somatic Cells.

Tsutomu Motohashi1, Hitomi Aoki2, Takahiro Kunisada2

  • 1Department of Molecular Design and Synthesis, Functional Biology Division, Gifu University Graduate School of Medicine, Gifu, Japan.

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|January 21, 2025
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Summary

Direct conversion bypasses pluripotency for cell reprogramming. Inducing epithelial-mesenchymal transition (EMT) significantly enhances direct conversion efficiency, showing promise for regenerative medicine.

Keywords:
EMTdirect conversionepithelial–mesenchymal transitionmammary epithelial cellsneural crest cells

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Regenerative Medicine

Background:

  • Direct conversion aims to reprogram somatic cells into target cells without a pluripotent stage.
  • Transcription factors (TFs) are crucial for directing cell fate during reprogramming.
  • Current methods often face limitations in achieving efficient direct conversion.

Purpose of the Study:

  • To investigate the role of epithelial-mesenchymal transition (EMT) in enhancing direct cell conversion.
  • To determine if inducing EMT improves the efficiency of converting somatic cells into specific target cells.

Main Methods:

  • Forced expression of specific transcription factors (TFs) including Sox10.
  • Induction of EMT in somatic cells using a combination of TFs (Snail1, Slug, Twist1, Tcfap2a) or TGF-β1.
  • Assessing direct conversion of keratinocytes and NMuMG cells into neural crest cells (NCCs).

Main Results:

  • EMT induction via TFs enhanced the direct conversion of mouse keratinocytes into NCCs.
  • EMT induction was necessary for the direct conversion of NMuMG cells into NCCs when combined with Sox10 expression.
  • TGF-β1-induced EMT followed by Sox10 expression successfully converted NMuMG cells into NCCs.

Conclusions:

  • Epithelial-mesenchymal transition (EMT) is advantageous for direct cell conversion.
  • Inducing EMT can overcome barriers to direct conversion, improving efficiency.
  • This finding has implications for advancing cell reprogramming technologies.