Genome organizer SATB1 function in salivary gland and development and growth

基因组组织者 SATB1 在唾液腺及其发育和生长中的功能

• 批准号: 10593721
• 负责人: Terumi Kohwi-Shigematsu
• 金额: $ 24.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593721
• 关键词: 3-Dimensional; Ablation; Acinar Cell; Adult; Ameloblasts; Architecture; Atlases; Autoimmune Diseases; Binding; Biological Process; Categories; Cell Cycle; Cell Differentiation process; Cell Lineage; Cell Maturation; Cell physiology; Cells; Cellular Structures; Chromatin; Data; Databases; Defect; Deglutition; Dental caries; Detection; Development; Digestion; Distal; Ductal Epithelial Cell; Embryo; Embryonic Development; Epidermis; Epigenetic Process; Epithelial Cells; Food; Foundations; Future; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genes; Genetic; Genetic Recombination; Genetic Transcription; Genome; Genomics; Gland; Growth; Growth and Development function; Head and Neck Cancer; Human Genome; Impairment; Infection prevention; Knockout Mice; Learning; Link; Location; Lubricants; Malignant Neoplasms; Metabolism; Modeling; Morphogenesis; Mus; National Institute of Dental and Craniofacial Research; Natural regeneration; Normal Cell; Nuclear; Oral cavity; Oral health; Organ; Osteoblasts; Phenotype; Production; Proliferating; Property; Proteins; RNA; Regulator Genes; Regulatory T-Lymphocyte; Role; Saliva; Salivary Glands; Sampling; Sjogren' s Syndrome; Stratum Basale; Structure; T-Cell Activation; T-Cell Depletion; T-Cell Development; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Therapeutic; Time; Tissues; Tooth structure; Transcript; Wild Type Mouse; aquaporin 5; base; body system; cell type; comparison control; design; effective therapy; experimental study; fetal; genomic locus; gland development; global run on sequencing; irradiation; mouse genome; novel; oral infection; postnatal; postnatal development; prevent; progenitor; programs; protein expression; recruit; satellite cell; stem cells; thymocyte; tissue culture; transcription factor; transcriptome sequencing

Project Summary/Abstract Salivary glands produce saliva, which facilitates digestion, acts as a lubricant to swallow foods, and prevents infections in oral cavity and tooth decay. Therefore, salivary gland function is important for oral health. Currently, there is no effective treatment for impaired salivary glands, which can be caused by therapeutic irradiation for the head and neck cancer or autoimmune diseases. To develop therapeutic strategies in the future, it is essential to understand the regulatory mechanisms underling development of salivary glands and their regeneration. Little is known about the regulators of gene expression, epigenetics and chromatin organization for salivary glands. Here, we will test a hypothesis that the genome organizer SATB1 is a critical regulator in salivary gland embryonic development, early postnatal growth and development, and function. This hypothesis is supported by SATB1 protein being expressed in both acinar and ductal cells at postnatal day 12 (P12) of wild-type mice and by detection of much smaller salivary glands in Satb1-/- mice compared to wild-type mice. We will identify SATB1 protein-expressing cells in SGs during embryonic and postnatal development. By genetic lineage tracing, we will study the role of SATB1 in acinar cell development and function. We will delete SATB1 in acinar cell- specific cell lineages (e.g. AQPT5+ or MIST1+ cells) at specific time points and determine the effects of SATB1 ablation in their descendants. Through these experiments, we will learn the roles of SATB1 in proliferation, morphogenesis, survival and growth during embryonic and early postnatal development. In addition, combining the lineage-tracing approach with Global run-on sequencing (GRO-seq), which captures nascent transcripts, we will identify genes regulated by SATB1 in a cell lineage-specific and stage-specific manner. We expect that results from these proposed experiments will uncover the critical contribution of SATB1 in salivary gland development, growth and function, and such information will likely provide the foundation for the future therapeutic design to promote salivary gland regeneration.

项目概要/摘要 唾液腺产生唾液，促进消化，充当吞咽食物的润滑剂，并防止 口腔感染和蛀牙。因此，唾液腺功能对于口腔健康非常重要。现在， 对于唾液腺受损没有有效的治疗方法，这可能是由治疗性辐射引起的 头颈癌或自身免疫性疾病。为了制定未来的治疗策略，至关重要 了解唾液腺发育及其再生的调节机制。小的 已知唾液腺基因表达、表观遗传学和染色质组织的调节因子。 在这里，我们将检验一个假设，即基因组组织者 SATB1 是唾液腺的关键调节因子 胚胎发育、出生后早期生长发育和功能。这个假设得到支持 野生型小鼠出生后第 12 天 (P12) 时 SATB1 蛋白在腺泡和导管细胞中表达 并通过检测 Satb1-/- 小鼠的唾液腺比野生型小鼠小得多。我们将确定 胚胎和出生后发育期间 SG 中 SATB1 蛋白表达细胞。通过基因谱系追踪， 我们将研究 SATB1 在腺泡细胞发育和功能中的作用。我们将删除腺泡细胞中的 SATB1- 在特定时间点对特定细胞谱系（例如 AQPT5+ 或 MIST1+ 细胞）进行分析，并确定 SATB1 的效果 消融他们的后代。通过这些实验，我们将了解SATB1在增殖中的作用， 胚胎和产后早期发育过程中的形态发生、存活和生长。此外，结合 使用全局连载测序 (GRO-seq) 的谱系追踪方法可捕获新生转录本，我们 将以细胞谱系特异性和阶段特异性的方式识别 SATB1 调节的基因。我们期望 这些实验的结果将揭示 SATB1 在唾液腺中的关键贡献 发育、成长和功能，这些信息可能为未来提供基础 促进唾液腺再生的治疗设计。