Targeting Gli1⁺ Cells for Oral Tissue Regeneration and Disease Treatment

The Hedgehog (Hh) signaling pathway plays an essential role in tissue development and homeostasis.Glioma-associated oncogene homolog 1 (Gli1) functions as a key transcription factor in Hedgehog signaling and acts as a direct target gene within this pathway. Gli1-positive (Gli1⁺) cells functions as pivotal effector cells of the Hh pathway, and play complex and critical roles in oral tissue development, homeostasis, post-injury repair, and oral disease progression. Recent advances in lineage-tracing techniques and single-cell RNA sequencing have deepened our understanding of Gli1⁺ cells, evolving from simple Hh pathway effectors to heterogeneous mesenchymal stem cell subsets, significantly enriching our knowledge of oral biology and pathology. This review systematically summarizes the fundamental characteristics of Gli1⁺ cells and their function in oral tissues.Their contributions to the initiation and progression of oral diseases, and the latest advances in Gli1⁺ cell-based tissue regeneration and disease treatment are also discussed. By integrating our findings on the biological properties of Gli1⁺ cells into their immunomodulatory roles in disease and Gli1⁺ cell-centered tissue regeneration strategies, we aim to provide a theoretical foundation for elucidating the cellular and molecular mechanisms that maintain oral tissue homeostasis. These insights pave the way for novel and precise therapeutic approaches in oral regenerative medicine.