NEMO Knockout Drives Variations in Gene Expression Regenerative Trajectory and Induces Chromatin Remodeling in murine muscle satellite cells during healing from traumatic injury

This study investigates the impact of NEMO knockout on healing from traumatic tibial injury within a murine muscle satellite cell model. NEMO KO mice were profiled via RNA-seq at 0, 2, 4, 7 days post cold shock injury (DPI). The largest transcriptional response was observed at 2 DPI within the WT model, but NEMO knockouts exhibited delayed myogenesis and muscle regenerative defects. Furthermore, it was observed that new fiber formation is defected upon transplantation of mutant derived MuSCs. mRNA profiling further suggested that loss of NF-kB signaling in MuSC’s in response to NEMO KO alters their ECM and cytokine secretome production. Additional profiling was performed at 2DPI via ATAC-seq within WT and NEMO mouse satellite cells, with observed changes in chromatin remodeling suggesting bidirectional MuSC-transcriptional regulator communication in skeletal muscle regeneration.