Cell proliferation-inducing protein 52/mitofilin is a surface antigen on undifferentiated human dental pulp stem cells.

Dental pulp is a soft tissue located inside the hard part of a tooth and it contains a stem cell population that can regenerate damaged dentin and/or pulp itself. Human dental pulp stem cells (hDPSCs) are multipotent adult stem cells that have the potential to be differentiated into a variety of cell types. Although cells cultured primarily from pulp tissue show heterogeneous phenotypes and variable efficiency in their dentinogenic differentiation, proper selection markers, which are specific to hDPSCs, are essential for the osteo/dentinogenic study of human dental pulp cells. We had previously screened a set of undifferentiation-specific cell surface antibodies of hDPSCs through decoy immunization. In this study, we show that one of these surface monoclonal antibodies, 3C4, is bound to intact pulp cells in a highly undifferentiation-specific manner. The surface antigen protein bound specifically to 3C4 antibody was identified through direct immunoprecipitation and liquid chromatography-tandem mass spectrometry as the cell proliferation-inducing protein 52/Mitofilin, which is a protein of the inner mitochondrial membrane and is a possible antagonist to maintaining mitochondrial activation during differentiation. The expression of mitofilin/3C4 antigen dramatically decreased during differentiation, and the depletion of mitofilin/3C4 antigen induced the expression of osteogenic/dentinogenic markers earlier than during normal differentiation. The 3C4-positive cells isolated by a magnetic-activated cell sorting system were differentiated with a higher efficiency than 3C4-negative cells. These results indicate that finding mitochondria-related stem cell markers is valuable to be able to identify and isolate primitive stem cells.