Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair

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.