770 Reprogramming of diabetic wounds by SOX2 triggers a pro-healing transcriptional signature

Diabetic foot ulcers (DFUs) are a severe complication of diabetes and common cause lower limb amputations associated with high mortality rate. We previously demonstrated that the transcription factor SOX2 establishes transcriptional network primes oral epithelium for rapid wound repair reprogrammed cutaneous keratinocytes to present accelerated resolution both in vitro vivo. However, mechanisms by which reverses effects during healing not known. used combination genomics human mouse datasets diabetic models identify molecules pathways responsible can be therapeutically targeted patients DFUs. Transcriptional profiling revealed inhibited DFUs compared acute wounds, contributing inhibition healing. In addition, we found reversed on significantly enhanced model Single cell analysis increased populations enriched genes involved migration proliferation processes (Hmgb, Stmn1, Ccnd1 Cdk1) stem (Krt15 Itga6) Sox2-overexpressing unwounded samples wild-type control mice. Additionally, keratinocyte differentiation markers loricrin filaggrin were downregulated Our data indicate Sox2 reprograms wounds enhance population activation trigger pro-healing response ultimately lead development novel therapies target SOX2-regulated restore