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

Schwann cells (SC) are crucial for physiological impulse conduction in peripheral nerves. They produce myelin, provide axonal metabolic support, and contribute to reparatory processes after nerve injury. During aging, peripheral nerves acquire myelin structural anomalies and are characterized by a lower fraction of SC and a higher fraction of senescent cells. All these changes correlate with impaired electrical conduction and consequently altered function of target tissues including skeletal muscle weakness and cardiac arrhythmia. To characterize and compare cardiac and sciatic nerve SC, as well as to explore age-related differences in SC abundance and their properties, we analyzed two TdTomato reporter mouse strains to isolate Sox10 or Plp1 expressing SC. We performed RNA-sequencing on sorted TdTomato-positive cells from the heart and sciatic nerve and validated transcriptomic findings at the protein level using immunofluorescence. Our data reveal a pro-angiogenic profile in cardiac SC when compared to sciatic SC. In addition, higher levels of neural-death associated genes and lower gene and protein expression levels of the fatty acid co-transporter Fabp4/FABP4 are detected in cardiac SC from old compared to young mice, suggesting an aging-related impairment of fatty acid transport. Finally, sciatic SC activate collagen remodeling and increased pro-inflammatory signaling including TNFα. Thus, cardiac and musculoskeletal SC have different expression profiles, and undergo different changes during aging, which may contribute to impaired nerve function in both organ systems.