Epigenetics of Dental Stem Cells: Markers and CP27 Function

描述(申请人提供)：发育和成熟的人类牙齿含有各种成体干细胞，可分化为牙周韧带、牙槽骨、牙骨质、牙髓和牙本质等牙科组织，也是持续补充高周转率组织(如牙周膜)的来源。干细胞的潜能、谱系分化和自我更新由染色质相关因子控制。精确了解染色质动力学的活性和调控机制，因为它们控制牙源性基因表达谱和谱系特征，将为破译牙齿组织的发育和再生潜力提供令人兴奋的机会。参与牙源性干细胞基因表达动态的染色质相关因子之一是SWR-Complex相关的转录辅助调节因子CP27。CP27在早期胚胎发育、轴向构型和牙齿发育过程中具有耐人寻味的时空表达模式(Diekwich和Luan 2002)。在初步研究中，我们发现缺乏CP27基因的胚胎直到囊胚期都发育正常，但在植入后不久就无法存活。CP27还影响组蛋白交换和ES细胞多能性网络的维持，包括转录调控因子，如Nanog和Sox2。为了解释CP27在染色质介导的基因调控机制中的作用，我们将组蛋白的变异型H2A.Z和SIN3共抑制物复合体SAP30确定为可能参与CP27介导的转录调控的潜在结合因子。证实了我们早期的工作，我们发现CP27在发育中的牙齿和成人牙源性干细胞中显著表达，并介导DLX3、Runx2和DSPP基因的表达。在目前的研究中，我们主要关注CP27基因在成人牙齿干细胞表观遗传调控中的作用。 与公共健康相关：牙齿的软组织含有许多具有非凡能力的细胞。这些细胞被称为成体干细胞。在这里，我们将进行一系列研究，以调查一种独特的基因产物(称为CP27)在牙齿形成中的作用。这些研究可能最终导致牙齿脱落和其他疾病的新疗法。

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.