Single-cell analysis reveals an indispensable role of SRSF2 in controlling fate of Myf5-expressing cells during skeletal muscle development

Skeletal muscle is an important tissue of animal body, which plays an important role in the process of motion, support and energy metabolism. Skeletal muscles are composed of striated myofibers bundles which formed during embryonic myogenesis and may undergo remodeling in the process of muscle regeneration after birth. SRSF2 is an important member of the splicing factor SR protein family. It plays an active role in transcription elongation, coupling transcription and splicing. A large number of studies have shown that it plays a key role in maintaining the normal development of thymus, heart and bone marrow. Here, we have used single cell RNA-seq and lineage analysis and gene knockout animal model to explore the regulation of splicing factor SRSF2 on myoblast cell fate and differentiation, as well as the mechanism in mouse skeletal muscle development. scRNA-seq: The SRSF2f/f mice were crossed with transgenic C57BL/6J mice expressing Cre recombinase driven by the Myf5 (myogenic factor 5) promoter to generate progeny (SRSF2f/w/Myf5-Cre). The SRSF2f/f mice were crossed with Rosa26-LSL-tdtomato (hereafter tdT) mice. After generated SRSF2f/f/tdT mice (both SRSF2 and tdT are homozygous). Next, mating SRSF2f/f/tdT with SRSF2f/w/Myf5-Cre mice to generate SRSF2f/f/Myf5-Cre/tdT mice. SRSF2f/w/Myf5-Cre/tdT littermates served as controls.