BioProject

We previously showed that STAT3 regulates myoblast differentiation in cell culture models, yet its role in adult muscle satellite cells (MuSC) in vivo was less well characterized. More...

We previously showed that STAT3 regulates myoblast differentiation in cell culture models, yet its role in adult muscle satellite cells (MuSC) in vivo was less well characterized. When Stat3 was conditionally deleted in MuSC, muscle development and adult MuSC formation were not affected. However, with repeated muscle injuries, the number of the quiescent MuSC in STAT3-null mice decreased and the regeneration was delayed, suggesting defective MuSC maintenance. Consistently, when we conditionally deleted Stat3 in MuSC of dystrophin-null mice, a mouse model for the fatal human Duchenne muscular dystrophy, the adult double knockout (dKO) mice displayed age-dependent reduction in the number of MuSC, and increase in muscle inflammation and fibrosis. Mechanistically, Stat3 ablation in dystrophin-null MuSC resulted in downregulation of several key myogenic genes including Pax7, upregulation of multiple pro-inflammatory and pro-fibrotic genes, and an increase in fibroadipogenic progenitor cells, which collectively contributed to defective MuSC maintenance and aggravated inflammation and fibrosis in dKO mice. Overall design: We generate a condition STAT3 knockout mice (dKO) with mdx background (Dystrophin null, mouse model for human Duchenne muscular dystrophy). Three pairs of dKO and mdx (control) mice were used for muscle satellite cell FACS sorting, followed by RNA extraction and sequencing library construction. Pair end RNA sequencing was performed with Illumina HiSeq system. Less...