Project: A single nucleus approach solving the role of MuSCs in myofiber rejuvenation

About

The rejuvenation effect of senescent cell removal from aged skeletal muscle can be partially attributed to beneficial effects on the skeletal muscle stem cells (MuSCs), which support myofiber homeostasis through fusion. To date it remains unknown to which cellular processes MuSCs contribute in order to promote myofiber homeostasis and rejuvenation. We address the role of the addition of MuSC-derived nuclei and mitochondria, and their associated DNA (mtDNA) in young and aged mice by combining cell and organelle tracing with single nucleus RNA sequencing (snRNAseq) and Spatial Transcriptomics (ST). Thereby, we will characterize the transcriptional contribution of ‘new’ MuSC-derived nuclei and mitochondria to adult myofibers; unravel the causal link between the transcriptional contribution of MuSCs to adult myofibers and the rate of MuSC fusion to myofibers; assess the contribution of ‘new’ MuSC-derived nuclei and mitochondria to the reversal of senescence-associated transcriptional alter