Identification of pro- and anti-tumorigenic signals from the injury microenvironment following depletion of Nf1 in myelinating Schwann cells

The loss of Nf1 in mSC is not sufficient to induce tumourigenesis, however, we found that after sciatic nerve injury, Nf1- deficient mSCs formed neurofibromas specifically at the wound site (Ribeiro et al., 2013). Remarkably, in contrast to the tumorigenic behaviour of Nf1- deficient SCs at the wound site, they behaved and repaired normally in the distal stump. This indicated that whereas the normal nerve environment suppresses neurofibroma formation, the injury site of the nerve is a tumour- promoting environment, fostering the development of neurofibromas. Using bulk RNA seq, comparing the injury site with the distal stump of Nf1 KO vs Control nerve fragments, we identified TGFB as pro-tumorigenic microenvironmental signal that is highly expressed by pro-tumorigenic macrophages at the site of injury in Nf1-Ko mice. Overall design: RNA seq profiling of regenerating nerve fragments of Nf1 KO and control mice at 14 days follwing nerve injury. 6 nerve fragments (each fragment had a size of 0.5mm) were combined from multiple mice for each sample. 3 independent samples were sequenced for each region and genotype of interest. Genotypes: P0-CreERT2:YFPfl/fl:Nf1+/+ (CTL) and P0-CreERT2:YFPfl/fl:Nf1fl/fl (loss of Nf1 im myelinating Schwann cells, Nf1 KO)