Dual-regulated myoD- and msx1-based interventions in C2C12-derived cells enable precise myogenic/osteogenic/adipogenic lineage control.
BACKGROUND
Advanced gene therapy, tissue engineering and biopharmaceutical manufacturing require sophisticated and well-balanced multiregulated multigene interventions to reprogram desired mammalian cell phenotypes.


METHODS
We have combined the streptogramin (PIP)- and tetracycline (TET)-responsive gene regulation systems for independent expression control of the differentiation determinants myoD and msx1 in C2C12-derived cells.


RESULTS
Different dual-regulated expression scenarios which induce either both, only one or none of the lineage control genes triggered differential differentiation and precise control of myogenic, osteogenic or adipogenic cell phenotypes.


CONCLUSIONS
Our findings substantiate the use of multiregulated multigene interventions in reprogramming cellular differentiation pathways in a desired manner.
Fux
Cornelia
C
Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Hoenggerberg, HPT D74, CH-8093 Zurich, Switzerland.
Langer
Dominik
D
Fussenegger
Martin
M
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001842:Bone and Bones / Q000166:cytology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000235:genetics*; D051957:MSX1 Transcription Factor; D051379:Mice; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D017570:MyoD Protein / Q000235:genetics*; D010011:Osteocytes / Q000166:cytology*; D010641:Phenotype; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D017570:MyoD Protein; D014157:Transcription Factors; D013752:Tetracycline