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: 7567145
• 负责人: Xianghong Luan
• 金额: $ 45.62万
• 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/7567145
• 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（由申请人提供）：发育和成熟的人牙具有多种成年干细胞，这些干细胞会引起分化的牙科组织，例如牙周韧带，牙槽骨，牙骨质，牙髓和牙本质，也是连续补充高扭转组织（如周期韧带）的资源。干细胞的效力，谱系分化和自我更新由染色质相关因子控制。在控制牙源性基因表达谱和谱系规范时，对染色质动力学活性和调节的机制的精确理解将为破译牙科组织的发育和再生潜力提供令人兴奋的机会。牙源性干细胞基因表达动力学中涉及的染色质相关因素之一是SWR复合物相关的转录共同调节剂CP27。 CP27在早期胚胎发育，轴向图案和牙齿发育过程中具有有趣的颞空间表达模式（Diekwisch and Luan 2002）。在初步研究中，我们发现缺乏CP27基因的胚胎正常发展到胚泡阶段，但在植入后不久就无法生存。 CP27还影响了组蛋白交换和ES细胞多能网络维护，包括转录调节剂，例如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共阻剂复合物SAP30被确定为可能涉及CP27介导的转录调控的潜在结合因子。确认我们的早期工作，我们发现CP27在发育和成年牙源性干细胞中显着表达，并介导DLX3，RUNX2和DSPP基因表达。在本研究中，我们关注CP27基因在成年牙科干细胞表观遗传调节中的作用。 公共卫生相关性：牙齿的软组织包含许多具有非凡能力的细胞。这些细胞称为成年干细胞。在这里，我们将进行一系列研究，以研究与牙齿形成有关的独特基因产物（称为CP27）的影响。这些研究最终可能导致牙齿和其他疾病丧失的新型治疗方法。