Rbfox2-dependent alternative splicing of Numb regulates Notch signaling during muscle stem cell activation

Satellite cells (SCs), or muscle stem cells, are the resident somatic stem cells responsible for skeletal muscle regeneration. Most SCs remain quiescent in resting adult muscles but can activate rapidly upon receiving a stimulus. While Rbfox2 has been reported to play an essential role in regulating myoblast differentiation, its role in the activation process of SCs remains elusive. To investigate the role of Rbfox2 during satellite cell activation, we freshly isolated satellite cells from Rbfox2 conditional knockout mice and performed RNA-seq to profile the transcriptome changes upon Rbfox2 knockout. Overall design: To investigate the role of Rbfox2 in SCs, we generated an Rbfox2 conditional knockout (cKO) mice by crossing Rbfox2 flox mice with Pax7CreERT2 mice, which enables the deletion of Rbfox2 specifically in SCs following tamoxifen injection. These mice were also crossed with Rosa26 EYFP mice to label Rbfox2-null SCs with yellow fluorescent protein (YFP). We then isolated satellite cells from Rbfox2 cKO and control mice, extracted the RNA and performed RNA-seq. Analysis is performed to identify differentially expressed genes and differentially spliced events.