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| Status |
Public on Apr 01, 2012 |
| Title |
HDAC inhibitors promote the pro-myogenic activity of Sca1-positive interstitial cells in regenerating dystrophic muscles |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
We report here on the identification and functional characterization of Sca1-positive muscle interstitial cells that contribute to regeneration or fibroadipogenic degeneration of dystrophic muscles and mediate the beneficial effects of HDAC inhibitors (HDACi) in mdx mice. We found that the phenotype adopted by these cells and their biological activity are influenced by changes in muscle environment. While Sca1-positive muscle interstitial cells from healthy muscles spontaneously adopt a fibro-adipogenic phenotype, Sca1-positive muscle interstitial cells isolated from dystrophic muscles of young mdx mice show a latent myogenic phenotype that is implemented by the exposure to HDACi. Co-culture assays in vitro and co-transplantation experiments in vivo demonstrate that HDACi also improve Sca1-positive muscle interstitial cell ability to enhance the differentiation potential of adjacent satellite cells. Importantly, HDACi-induced myogenic phenotype and pro-regeneration activity were not observed in Sca1-positive muscle interstitial cells isolated from muscles of old mdx mice. The different phenotype of Sca1-positive muscle interstitial cells from mdx mice at different stages of disease progression correlated with the stage-dependent beneficial effect of HDACi, which were effective only at early stages of disease. Transplantation of Sca1-positive muscle interstitial cells isolated from regenerating young muscles into muscles of old mdx mice restored HDACi ability to increase myofiber size. These results indicate that Sca1-positive muscle interstitial cells are key cellular determinants of disease progression and mediate the beneficial effect of HDACi in a mouse model of muscular dystrophy.
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| Overall design |
Isolation of Sca1+ muscle interstitial cells from TSA treated DMD/MDX mice and MuSc from DMD/MDX mice
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| Citation missing |
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| |
| Submission date |
Jan 04, 2012 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Roy M Williams |
| E-mail(s) |
rwillia@scripps.edu
|
| Organization name |
The Scripps Research Institute
|
| Department |
Regenerative Medicine
|
| Lab |
Loring
|
| Street address |
3030 Science Park Road
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
|
| Samples (5)
|
| GSM856083 |
Sca1+ muscle interstitial cells isolated from veichle treated MDX mice (45 days) replicate 1 |
| GSM856084 |
Sca1+ muscle interstitial cells isolated from veichle treated MDX mice (45 days) replicate 2 |
| GSM856085 |
Sca1+ muscle interstitial cells isolated from TSA treated MDX mice (45 days) replicate 1 |
| GSM856086 |
Sca1+ muscle interstitial cells isolated from TSA treated MDX mice (45 days) replicate 2 |
| GSM856087 |
MuSC cells isolated from veichle treated MDX mice (45 days) replicate 1 |
|
| Relations |
| BioProject |
PRJNA150141 |
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