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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kabadi, AM; Thakore, PI; Vockley, CM; Ousterout, DG; Gibson, TM; Guilak, F; Reddy, TE; Gersbach, CA

Published Date

  • June 2015

Published In

Volume / Issue

  • 4 / 6

Start / End Page

  • 689 - 699

PubMed ID

  • 25494287

Pubmed Central ID

  • 25494287

Electronic International Standard Serial Number (EISSN)

  • 2161-5063

International Standard Serial Number (ISSN)

  • 2161-5063

Digital Object Identifier (DOI)

  • 10.1021/sb500322u

Language

  • eng