GSE104324
Soluble Neuregulin1 is a negative regulator of myelination
Peripheral nerves are characterized by the ability to regenerate after injury. The activity of Schwann cells is fundamental for all steps of peripheral nerve regeneration: immediately after injury they de-differentiate, remove myelin debris, proliferate and repopulate the injured nerve. Neuregulin1 (NRG1) is a factor strongly up-regulated and released by Schwann cells immediately after nerve injury, known to play an important role for their de-differentiation, proliferation and survival. Nevertheless, up to now, the global analysis of the genes regulated by NRG1 was not performed. For this reason, we planned a deep RNA sequencing to generate a transcriptome database and identify all the genes regulated following stimulation of primary adult rat Schwann cells with soluble recombinant NRG1. Interestingly, the gene ontology analysis of the transcriptome shows that NRG1 regulates genes belonging to categories strongly regulated in the peripheral nerve immediately following injury. In particular, NRG1 strongly inhibits the expression of genes involved in myelination and in glial cell differentiation, suggesting that NRG1 plays a fundamental role in the de-differentiation (or “trans-differentiation”) process of Schwann cells from a myelinating to a repair phenotype. Moreover, NRG1 inhibits genes involved in the apoptotic process, therefore promoting cell survival, and up-regulates genes positively regulating the ribosomal RNA processing, thus suggesting that NRG1 actively stimulates new protein expression.  This transcriptome analysis demonstrates that NRG1, which is strongly up-regulated immediately after injury, drives the expression of many important genes, thus playing a major role in the regeneration process. Overall design: Examination of genes regulated in Schwann cells after 6 hour stimulation with 10nM soluble Neuregulin1beta1