PITX2 Enhances the Regenerative Potential of Dystrophic Skeletal Muscle Stem Cells

Publication date: 10 April 2018 Source:Stem Cell Reports, Volume 10, Issue 4 Author(s): Daniel Vallejo, Francisco Hernández-Torres, Estefanía Lozano-Velasco, Lara Rodriguez-Outeiriño, Alejandra Carvajal, Carlota Creus, Diego Franco, Amelia Eva Aránega Duchenne muscular dystrophy (DMD), one of the most lethal genetic disorders, involves progressive muscle degeneration resulting from the absence of DYSTROPHIN. Lack of DYSTROPHIN expression in DMD has critical consequences in muscle satellite stem cells including a reduced capacity to generate myogenic precursors. Here, we demonstrate that the c-isoform of PITX2 transcription factor modifies the myogenic potential of dystrophic-deficient satellite cells. We further show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells, but importantly also increasing dystrophin-positive (revertant) myofibers by regulating miR-31. These PITX2-mediated effects finally lead to improved muscle function in dystrophic (DMD/mdx) mice. Our studies reveal a critical role for PITX2 in skeletal muscle repair and may help to develop therapeutic strategies for muscular disorders. Teaser Vallejo et al. show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells but importantly also increasing dystrophin-positive...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research