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Chem Biol. 2011 Sep 23;18(9):1153-66. doi: 10.1016/j.chembiol.2011.07.012.

Inhibitors of tyrosine phosphatases and apoptosis reprogram lineage-marked differentiated muscle to myogenic progenitor cells.

Author information

1
Department of Bioengineering, University of California, Berkeley, CA 94720, USA. ppaliwal@berkeley.edu

Abstract

Muscle regeneration declines with aging and myopathies, and reprogramming of differentiated muscle cells to their progenitors can serve as a robust source of therapeutic cells. Here, we used the Cre-Lox method to specifically label postmitotic primary multinucleated myotubes and then utilized small molecule inhibitors of tyrosine phosphatases and apoptosis to dedifferentiate these myotubes into proliferating myogenic cells, without gene overexpression. The reprogrammed, fusion competent, muscle precursor cells contributed to muscle regeneration in vitro and in vivo and were unequivocally distinguished from reactivated reserve cells because of the lineage marking method. The small molecule inhibitors downregulated cell cycle inhibitors and chromatin remodeling factors known to promote and maintain the cell fate of myotubes, facilitating cell fate reversal. Our findings enhance understanding of cell-fate determination and create novel therapeutic approaches for improved muscle repair.

PMID:
21944754
PMCID:
PMC3183467
DOI:
10.1016/j.chembiol.2011.07.012
[Indexed for MEDLINE]
Free PMC Article
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