Spatially resolved transcriptomics reveals innervation-responsive functional cluster in skeletal muscle.

Striated muscle is a highly organized structure composed by well-defined anatomical domains with integrated but distinct assignments. Indeed, the lack of a direct correlation between tissue architecture and gene expression has thus far limited our understanding of how each unit responds to physio-pathologic contexts. Here, we show how the combined use of spatially resolved transcriptomics and immunofluorescence can bridge this gap by enabling the unbiased identification of such domains and the characterization of their response to external perturbations. Using a spatiotemporal analysis, we followed the changes in the transcriptomics profile of specific domains in muscle in a model of denervation. Furthermore, our approach allowed us to identify the spatial distribution and nerve dependence of atrophic signalling pathway and polyamine metabolism to glycolytic fibres. Indeed, we demonstrate a pronounced alteration of polyamine homeostasis upon denervation. Overall design: Spatial Transcriptomics analysis of wildtype murine Tibialis Anterior and Extensor digitorum longus prior and after Nerve Crush (3 days and 30 days )