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Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain.

Publication ,  Journal Article
Kabadi, AM; Thakore, PI; Vockley, CM; Ousterout, DG; Gibson, TM; Guilak, F; Reddy, TE; Gersbach, CA
Published in: ACS Synth Biol
June 19, 2015

Genetic reprogramming holds great potential for disease modeling, drug screening, and regenerative medicine. Genetic reprogramming of mammalian cells is typically achieved by forced expression of natural transcription factors that control master gene networks and cell lineage specification. However, in many instances, the natural transcription factors do not induce a sufficiently robust response to completely reprogram cell phenotype. In this study, we demonstrate that protein engineering of the master transcription factor MyoD can enhance the conversion of human dermal fibroblasts and adult stem cells to a skeletal myocyte phenotype. Fusion of potent transcriptional activation domains to MyoD led to increased myogenic gene expression, myofiber formation, cell fusion, and global reprogramming of the myogenic gene network. This work supports a general strategy for synthetically enhancing the direct conversion between cell types that can be applied in both synthetic biology and regenerative medicine.

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Published In

ACS Synth Biol

DOI

EISSN

2161-5063

Publication Date

June 19, 2015

Volume

4

Issue

6

Start / End Page

689 / 699

Location

United States

Related Subject Headings

  • Protein Structure, Tertiary
  • Protein Engineering
  • MyoD Protein
  • Muscle Fibers, Skeletal
  • Muscle Development
  • Molecular Sequence Data
  • Lentivirus
  • Humans
  • HEK293 Cells
  • Genetic Vectors
 

Citation

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Kabadi, A. M., Thakore, P. I., Vockley, C. M., Ousterout, D. G., Gibson, T. M., Guilak, F., … Gersbach, C. A. (2015). Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain. ACS Synth Biol, 4(6), 689–699. https://doi.org/10.1021/sb500322u
Kabadi, Ami M., Pratiksha I. Thakore, Christopher M. Vockley, David G. Ousterout, Tyler M. Gibson, Farshid Guilak, Timothy E. Reddy, and Charles A. Gersbach. “Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain.ACS Synth Biol 4, no. 6 (June 19, 2015): 689–99. https://doi.org/10.1021/sb500322u.
Kabadi AM, Thakore PI, Vockley CM, Ousterout DG, Gibson TM, Guilak F, et al. Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain. ACS Synth Biol. 2015 Jun 19;4(6):689–99.
Kabadi, Ami M., et al. “Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain.ACS Synth Biol, vol. 4, no. 6, June 2015, pp. 689–99. Pubmed, doi:10.1021/sb500322u.
Kabadi AM, Thakore PI, Vockley CM, Ousterout DG, Gibson TM, Guilak F, Reddy TE, Gersbach CA. Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain. ACS Synth Biol. 2015 Jun 19;4(6):689–699.
Journal cover image

Published In

ACS Synth Biol

DOI

EISSN

2161-5063

Publication Date

June 19, 2015

Volume

4

Issue

6

Start / End Page

689 / 699

Location

United States

Related Subject Headings

  • Protein Structure, Tertiary
  • Protein Engineering
  • MyoD Protein
  • Muscle Fibers, Skeletal
  • Muscle Development
  • Molecular Sequence Data
  • Lentivirus
  • Humans
  • HEK293 Cells
  • Genetic Vectors