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Myogenic program induction in mature fat tissue (with MyoD expression).

Y C Kocaefe1, D Israeli, M Ozguc

  • 1Genethon CNRS UMR8115 1 bis rue de l'Internationale 91002 Evry cedex, France. kocaefe@hacettepe.edu.tr

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MyoD gene transfer can reprogram mature fat cells into muscle cells. This MyoD-induced transdifferentiation in adipocytes occurs without cell division and is well-tolerated in vivo.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Regenerative Medicine

Background:

  • MyoD is a key transcription factor regulating muscle development.
  • Mature adipocytes are terminally differentiated cells with limited plasticity.
  • Understanding cell fate conversion is crucial for regenerative therapies.

Purpose of the Study:

  • To investigate the potential of MyoD gene transfer to induce myogenic transdifferentiation in mature adipocytes.
  • To characterize the morphological and molecular changes during adipocyte-to-muscle conversion.
  • To assess the feasibility and tolerance of this process in vitro and in vivo.

Main Methods:

  • Organotypic cultures of fat tissue and long-term in vitro adipocyte cultures.
  • MyoD gene transfer into mature adipocytes.
  • In vivo studies using rat interscapular and inguinal fat pads.
  • Analysis of morphological changes, fat content, and protein expression (muscle and adipocyte markers).

Main Results:

  • MyoD induced significant morphological changes in adipocytes, including fat loss and acquisition of a fusiform shape.
  • Transdifferentiated cells exhibited expression of muscle lineage proteins, co-existing with adipocyte markers initially.
  • In vivo studies confirmed muscle protein expression and gradual reduction in fat content and adipocyte markers over time.
  • The transdifferentiation process did not necessitate cell cycle progression and was well-tolerated by mature adipocytes.

Conclusions:

  • MyoD gene transfer effectively induces myogenic transdifferentiation in mature adipocytes.
  • Adipocyte-to-muscle conversion is achievable in terminally differentiated cells without cell division.
  • This study demonstrates a potential strategy for generating muscle cells from adipocytes, relevant for regenerative medicine.