AbstractObjectivesThe microenvironmental niche plays the key role for maintaining the cell functions. The stem cells from apical papilla (SCAPs) are important for tooth development and regeneration. However, there is limited knowledge about the key factors in niche for maintaining the function ofSCAPs. In this study, we analyse the gene expression profiles between apical papilla tissues,SCAPs andSCAPs cell sheet to identify the key genes inSCAPs niche.Materials and methodsMicroarray assays and bioinformatic analysis were performed to screen the differential genes between apical papilla tissues andSCAPs, andSCAPs andSCAPs cell sheet. Recombinant humanBMP6 protein was used inSCAPs. ThenCCK‐8 assay,CFSEassay, alkaline phosphatase activity, alizarin red staining, quantitative calcium analysis and real‐time reverse transcriptase‐polymerase chain reaction were performed to investigate the cell proliferation and differentiation potentials ofSCAPs.ResultsMicroarray analysis found that 846 genes were up‐regulated and 1203 genes were down‐regulated inSCAPs compared with apical papilla tissues. While 240 genes were up‐regulated and 50 genes were down‐regulated inSCAPs compared to inSCAPs cell sheet. Moreover, only 31 gene expressions in apical papilla tissues were recovered in cell sheet compared withSCAPs. Bioinformatic analysis identified thatTGF‐β,WNTandMAPKsignalling pathways may play an important role inSCAPs niche. Based on the analysis, we identified one key growth factor in niche,BMP6, which could enhance the cell proliferation, the osteo/dentinogenic, neurogenic and angiogenic differentiation potentials ofSCAPs.ConclusionsOur results provided insight into the mechanisms of the microenvironmental niche which regulate the function ofSCAPs, and identified the key candidate genes in niche to promote mesenchymal stem cells‐mediated dental tissue regeneration.