1. Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain
- Author
-
Pratiksha I. Thakore, Charles A. Gersbach, Farshid Guilak, Christopher M. Vockley, David G. Ousterout, Ami M. Kabadi, Timothy E. Reddy, and Tyler M. Gibson
- Subjects
Letter ,Genetic Vectors ,Molecular Sequence Data ,Muscle Fibers, Skeletal ,Biomedical Engineering ,regenerative medicine ,Biology ,MyoD ,Muscle Development ,Protein Engineering ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,03 medical and health sciences ,Transactivation ,0302 clinical medicine ,MyoD Protein ,Humans ,Cell Lineage ,Gene Regulatory Networks ,Amino Acid Sequence ,Transcription factor ,transcription factor ,mesenchymal stem cell ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Myogenesis ,Transdifferentiation ,Lentivirus ,adipose stem cell ,General Medicine ,Dermis ,Fibroblasts ,Cellular Reprogramming ,Molecular biology ,3. Good health ,Cell biology ,Protein Structure, Tertiary ,muscle cell therapy ,Adult Stem Cells ,HEK293 Cells ,genetic reprogramming ,Gene Expression Regulation ,Cell Transdifferentiation ,myogenesis ,Reprogramming ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2014