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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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目总结/文摘