Epigenetics of Dental Stem Cells: Markers and CP27 Function

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DESCRIPTION (provided by applicant): Developing and mature human teeth harbor a variety of adult stem cells that give rise to differentiated dental tissues such as periodontal ligament, alveolar bone, cementum, pulp, and dentin, and also serve as a resource for the continuous replenishment of high-turnover tissues such as the periodontal ligament. Potency, lineage differentiation, and self-renewal of stem cells are controlled by chromatin-associated factors. A precise understanding of the mechanisms underlying the activity and regulation of chromatin dynamics as they control odontogenic gene expression profiles and lineage specification will provide an exciting opportunity toward deciphering the developmental and regenerative potential of dental tissues. One of the chromatin-associated factors involved in odontogenic stem cell gene expression dynamics is the SWR-complex associated transcriptional co-regulator CP27. CP27 features an intriguing temporo-spatial expression pattern during early embryonic development, axial patterning, and tooth development (Diekwisch and Luan 2002). In preliminary studies, we found that embryos lacking the CP27 gene developed normally until blastocyst stage, but failed to survive shortly after implantation. CP27 also affected histone exchange and ES cell pluripotency network maintenance, including transcriptional regulators such as Nanog and Sox2. In order to explain the effect of CP27 on chromatin-mediated gene regulation mechanisms, the variant histone H2A.Z and the SIN3 co-repressor complex subunit SAP30 were identified as potential binding factors that might be involved in CP27 mediated transcriptional regulation. Confirming our earlier work, we found CP27 to be prominently expressed in developing teeth and adult odontogenic stem cells and to mediate DLX3, Runx2 and DSPP gene expression. In the present study we are focusing on the role of the CP27 gene in the epigenetic regulation of adult dental stem cells. PUBLIC HEALTH RELEVANCE: The soft tissues of teeth contain a number of cells with extraordinary capabilities. These cells are called adult stem cells. Here we will conduct a series of studies to investigate the effect of a unique gene product (called CP27) involved in the formation of teeth. These studies might eventually lead to novel cures for the loss of teeth and other diseases.