Single-cell RNAseq analysis of Nf1-deficient Prss56-derived cells from spinal columns of young and old mice

Neurofibromatosis type 1 (NF1) is a genetic disorder affecting 1 in 3000 people due to heterozygous mutations in the NF1 gene. Patients with NF1 can develop multiple symptoms, such as neurofibromas, skin hyperpigmentation, and bone abnormalities, including tibial pseudarthrosis and spine deformity. Here, we aimed to elucidate the cellular origin and pathogenic mechanism of NF1 spine deformity. Prss56-Nf1 knockout (KO) mouse is a model that recapitulates neurofibromas and pseudarthrosis by carrying Nf1 gene inactivation in Prss56-expressing boundary cap (BC) cells, a neural crest subset, and their derivatives. Through transcriptomics analysis, we explored the molecular changes that occur through time in Prss56-derived cells populating the vertebral column of Prss56-Nf1 KO mice. Overall design: Prss56-derived tdTom+ cells were isolated by FACS from digested vertebrae of 3 month-old or 12-16 month-old from Prss56Cre/Cre;R26tdTom/tdTom;Nf1fl/fl and Prss56Cre/+;R26tdTom/tdTom;Nf1+/+.