Enhanced MyoD-Induced Transdifferentiation to a Myogenic Lineage by Fusion to a Potent Transactivation Domain.

TitleEnhanced MyoD-Induced Transdifferentiation to a Myogenic Lineage by Fusion to a Potent Transactivation Domain.
Publication TypeJournal Article
Year of Publication2015
AuthorsAM Kabadi, PI Thakore, CM Vockley, DG Ousterout, TM Gibson, F Guilak, TE Reddy, and CA Gersbach
JournalACS Synthetic Biology
Volume4
Issue6
Start Page689
Pagination689 - 699
Date Published06/2015
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.

DOI10.1021/sb500322u
Short TitleACS Synthetic Biology