Myeloid-to-mesenchymal NGF-p75 signaling coordinates cell migration during bone repair [scRNA-seq]

The cranial sutures are fibrous joints containing skeletal progenitor cells, which maintain homeostasis of the uninjured skull or participate in healing the skull after injury. Nerve growth factor (NGF) via its high-affinity receptor tropomyosin receptor kinase A (TrkA) regulates skeletal re-innervation, which is essential for later elements of bone repair, including revascularization and bone matrix deposition. However, emerging evidence suggests that NGF signaling may have more pleiotropic effects in bone repair than previously considered. In addition to induction of nerve ingrowth and promotion of nerve survival, pro-NGF may bind to its low-affinity receptor Ngfr (p75, Cd271), which is present in a variety of mesenchymal cells. p75 expression has been correlated to cell migration and invasion in multiple cell types. NGF binding to the p75 receptor stimulates migration and initiates recruitment of various adaptors, which activate NF-κB, RhoA, and c-Jun N-terminal kinase (JNK) signaling. In this study, single cell transcriptomics highlights altered signaling pathway activation and impaired cellular migration with p75 conditional gene deletion in PDGFRα-expressing cells. 2 Total samples were analyzed comparing mRNA from p75 floxed mice (p75fl/fl) and p75 conditional knockout mice (p75PDGFRα).