BioProject

The healing of bone injury begins with the release of microenvironment signals and regulation ofcell identity transformation. More...

The healing of bone injury begins with the release of microenvironment signals and regulation ofcell identity transformation. Schwann cells (SCs) of peripheral nerve play a critical role in the earlystage of vascular remodeling and bone regeneration. However, how SCs respond to injury andinitiate the vascularized osteogenesis remains incompletely understood. Here, by employing single-cell transcriptional profiling combined with lineage-specific tracing models, we uncovered that asubset of Gli1+ mesenchymal stromal cells (MSCs) undergoing injury-induced glia-to-MSCtransition (GMT) contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly, our data demonstrated that the Sonic hedgehog (Shh) signaling was responsible for theGMT initiation, which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shhenhancers. Collectively, these findings depict an injury-specific niche signal-mediated SCstransition towards Gli1+ MSCs and may be instructive for approaches to promote bone regenerationduring aging or other bone diseases. Overall design: Mice were divided into sham group and denervation group.For IAN denervation, one-side inferior alveolar nerves were severed using microsurgery.In contrast, sham surgeries involved the same dissection and retraction steps but preserved the integrity of the IAN.A postoperative period of at least two weeks was allotted to ensure complete nerve degeneration following denervation, before proceeding with any subsequent experiments.Three Sham or Denervation 12-week-old male C57BL/6J wild-type mice were combined to extract single-cell suspensions.Three days after all 3 molars tooth extraction, mandibles were meticulously isolated under a stereomicroscope.Soft tissues and jaw bone around the incisor and behind condyle were cut off to obtain the region of tooth extraction socket tissues.Tissues were digested for single-cell suspension. Less...