Pax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage.
Mesenchymal stem cells (MSCs) residing within the bone marrow (BM) differentiate into multiple lineages, including fat, bone, and cartilage. Because MSCs are multipotent and have a great capacity to be expanded in vitro, these cells are an attractive candidate for clinical applications to repair or regenerate damaged tissues of mesenchymal origin. However, application of MSCs to muscle degenerative diseases has been hampered by the poor differentiation of MSCs into the muscle lineage. To date most methods require the presence of strong non-physiological agents, such as azacytidine. In the present study we explored the potential of Pax3, the master regulator of the embryonic myogenic program, to promote myogenic differentiation from MSCs. Our results clearly demonstrate that Pax3 promotes the differentiation of MSCs towards the myogenic lineage, which occurs at the expense of other mesenchymal lineages including fat, bone, and cartilage. This effect is cell type-selective since Pax3 overexpression in endothelial cells fails to promote myogenesis. These results highlight the potential of regulating transcriptional pathways to direct differentiation of adult stem cells.
Gang
Eun Ji
EJ
Department of Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9133, USA.
Bosnakovski
Darko
D
Simsek
Tugba
T
To
Khai
K
Perlingeiro
Rita C R
RC
D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D020219:Chondrogenesis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D032342:Muscle Cells / Q000166:cytology*; D010012:Osteogenesis; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*
D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C068686:Pax3 protein, mouse