BMP4 dose dictates lineage specification bias in human periodontal ligament stem cells.

INTRODUCTION: Periodontal ligament stem cells (PDLSCs) represent a promising therapeutic cell source for regenerating periodontal tissues impaired by disease. While exogenous BMP4 has been used to induce human PDLSC differentiation into distinct periodontal cell lineages, its dose-dependent effects on lineage specification remain poorly understood. METHODS: Here, we systematically investigated how BMP4 dosage modulates human PDLSC differentiation toward osteogenic and tenogenic lineages using single-cell RNA sequencing and RESULTS: Single-cell transcriptomic analysis revealed that endogenous CONCLUSION: These findings demonstrate that precise BMP4 dosage regulation dictates PDLSC differentiation outcomes, providing crucial insights for optimizing PDLSC-based periodontal regenerative therapies.