Epigenetics of Dental Stem Cells: Markers and CP27 Function

牙干细胞的表观遗传学：标记物和 CP27 功能

• 批准号: 7896681
• 负责人: Xianghong Luan
• 金额: $ 45.2万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7896681
• 关键词: Adult; Affect; Binding; Biological Assay; Cell Count; Cell Lineage; Cell Maintenance; Cells; Chromatin; Co-Immunoprecipitations; Complex; Dental; Dental Cementum; Dental Pulp; Dental Sac; Dentin; Development; Disease; Embryo; Embryonic Development; Epigenetic Process; Gene Expression; Gene Expression Regulation; Genes; Genetic; Histone Acetylation; Histones; Human; Lead; Maintenance; Mediating; Microarray Analysis; Modification; Molecular Profiling; Mus; Nuclear; Pattern; Periodontal Ligament; Play; Promoter Regions; Proteins; Regulation; Research; Resources; Role; Series; Staging; Stem cells; System; Testing; Tetanus Helper Peptide; Therapeutic; Tissues; Tooth Loss; Tooth structure; Transcriptional Regulation; Variant; Work; adult stem cell; alveolar bone; blastocyst; chromatin immunoprecipitation; embryonic stem cell; implantation; mutant; novel; pluripotency; postnatal; promoter; public health relevance; regenerative; self-renewal; soft tissue

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.

描述（申请人提供）：发育成熟的人类牙齿拥有多种成体干细胞，这些干细胞可以分化成牙周韧带、牙槽骨、牙骨质、牙髓和牙本质等牙齿组织，也可以作为牙周韧带等高周转率组织的持续补充资源。干细胞的效力、谱系分化和自我更新是由染色质相关因子控制的。染色质动力学控制牙源性基因表达谱和谱系规范，对其活性和调控机制的精确理解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复合物相关转录共调控因子CP27。CP27在早期胚胎发育、轴向模式和牙齿发育过程中具有有趣的时空表达模式（Diekwisch和Luan 2002）。在初步研究中，我们发现缺乏CP27基因的胚胎在囊胚期之前发育正常，但在着床后不久就不能存活。CP27还影响组蛋白交换和ES细胞多能性网络的维持，包括转录调节因子如Nanog和Sox2。为了解释CP27对染色质介导的基因调控机制的影响，变异组蛋白H2A。Z和SIN3共抑制复合物亚基SAP30被确定为可能参与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体牙源性干细胞中显著表达，并介导DLX3， Runx2和DSPP基因表达。在目前的研究中，我们主要关注CP27基因在成体牙干细胞表观遗传调控中的作用。