Multi-level expression profiling of cardiac and musculoskeletal Schwann cells, in young and old mice.

Schwann cells (SC) are crucial for normal conduction in peripheral nerves. They produce myelin, provide axonal metabolic support, and activate a reparatory phenotype after nerve injury. During aging, peripheral nerves present abnormal myelin, reduced SC density, and increased senescence. All these changes induce abnormal electrical conduction and consequently impaired function of target tissues, like for example, skeletal muscle weakness and cardiac arrhythmia. In order to understand differences between cardiac and sciatic nerve (SN) SC, as well as to explore age-related changes of function, we characterize two inducible CRE mouse models, Sox10CreERT2 and Plp1CreERT, to genetically trace SC by combining them with TdT reporter mice. To do this, we use FACS to sort tdt (+) cells from the heart and SN, and further perform RNAseq to characterize their gene expression. Complementarily, we confirm protein expression using immunofluorescence. Our data indicates that cardiac SC detected using the Plp1CreERT model are enriched for MPZ (+) myelinating SC. In addition, we describe a novel pro-angiogenic function for cardiac SC in young mice. Furthermore, we found that during aging, SC from SN activate collagen remodeling and secrete pro-inflammatory signals like TNFa. Finally, we detect increased neural-death associated genes in cardiac SC, which also have less expression of the fatty acid co-transporter FABP4, suggesting abnormal myelin formation. Thus, cardiac and musculoskeletal SC have different expression profiles, and undergo different but remarkable changes during aging, which can contribute to abnormal nerve function. Overall design: To study sciatic and cardiac Schwann cells, we used two different inducible CRE models crossed with a TDT reporter mouse line. We harvested the heart and the sicatic nerve from young (2-3 months old) and old (20-24 months old) Sox10CRERT2;R26TDT and Plp1CREER;R26TDT. We FACSed viable TDT+ cells and performed RNAseq from them. Then compared conditions (tissue/model/age)