Fatty acid synthesis in satellite glial cell promotes regenerative growth in sensory neurons

Oshri Avraham, Pan-Yue Deng, Sara Jones, Rejji Kuruvilla, Clay F. Semenkovich, Vitaly A. Klyachko, Valeria Cavalli

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Received Date: 10th January 20

Peripheral sensory neurons switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, undergo injury-evoked transcriptional changes to contribute to nerve regeneration remains unexplored. This is largely due to the lack of molecular and genetic tools to study SGC. Using a single cell RNAseq approach to define the transcriptional profile of SGC in naïve and injured conditions, we reveal that these cells are distinct from Schwan cells and share similarities with astrocytes. We find that nerve injury elicits gene expression changes in SGC, which are related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARa) signaling. Conditional deletion of Fatty acid synthase (Fasn), the committed  enzyme in de novo fatty acid synthesis, in SGC, impairs axon regeneration. The PPARa agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC, indicating that PPARa functions downstream of fatty acid synthesis in SGC to promote axon regeneration. These results identify fatty acid synthesis in SGC as a fundamental novel mechanism mediating axon regeneration in adult peripheral nerves. These results also highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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