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Single-Cell Virtual Perturbation Screening Identifies STAT3 as a Key Regulator of Dentinogenesis - PubMed

6 hours ago
  • #dentinogenesis
  • #single-cell
  • #STAT3
  • The study used single-cell virtual perturbation screening to identify STAT3 as a key regulator of dentinogenesis, or dentine formation.
  • EFNB2+ mesenchymal cells were identified as primary progenitors in the odontogenic lineage through single-cell transcriptional analysis.
  • In silico perturbations predicted that STAT3 ablation disrupts the developmental vector field, redirecting mesenchymal precursor fate away from the odontoblast lineage.
  • Functional validation with shRNA silencing, pharmacological modulation, and conditional knockout mice confirmed STAT3's essential role in dental mesenchymal cell proliferation, differentiation, and dentine formation.
  • Mechanistically, STAT3 directly binds to the WNT2B promoter to activate the Wnt/β-catenin signaling pathway, and WNT2B overexpression partially rescues defects from STAT3 inactivation.