Sox11 is enriched in myogenic progenitors but dispensable for development and regeneration of skeletal muscle

Abstract

AbstractTranscription factors (TFs) play key roles in regulating the differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment ofSox11mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data,Sox11levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate thatSox11expression is reduced in aged MuSCs. Age-related decline ofSox11expression is associated with reduced chromatin contacts within the topologically associated domains. Unexpectedly, Myod1Cre-driven deletion ofSox11in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreERor Rosa26CreERdriven (MuSC-specific or global) deletion ofSox11in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remain to be elucidated.