Underlying Molecular Mechanisms of Gliogenesis and Gliomagenesis in the Central Nervous System

中枢神经系统胶质细胞生成和胶质瘤发生的潜在分子机制

基本信息

批准号：
9126619
负责人：
Tou Yia Vue
金额：
$ 8.22万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9126619
关键词：
Address Amyotrophic Lateral Sclerosis Animal Model Animals Astrocytes Astrocytoma Autistic Disorder Automobile Driving BHLH Protein Brain Brain Neoplasms Cells ChIP-seq Cognitive DNA Binding Data Data Analyses Development Disease Ensure Epilepsy Faculty Gene Expression Gene Targeting Generations Genetic Genetic Techniques Glioblastoma Glioma Gliomagenesis Goals Health Heterogeneity Lead LoxP-flanked allele Malignant neoplasm of brain Mentors Molecular Molecular Profiling Multiple Sclerosis Mus Neuraxis Neuroglia Oligodendroglia Oncogenes Phase Positioning Attribute Process Proliferating Property Prosencephalon Regenerative Medicine Research Role Schizophrenia Sclerosis Secure Spinal Spinal Cord Stem cells Survival Rate Techniques Technology Testing Tetanus Helper Peptide To specify Training Viral Viral Vector Work brain behavior cell type combat combinatorial differential expression epidermal growth factor receptor VIII genetic regulatory protein genome-wide glial cell development gliogenesis gray matter improved in vivo insight malignant neurologic neoplasms men migration mouse model neoplastic cell nerve stem cell nervous system disorder new therapeutic target next generation sequencing oligodendrocyte lineage oligodendrocyte precursor precursor cell progenitor recombinase skills spinal cord white matter subventricular zone transcriptome sequencing tumor tumor growth tumorigenesis white matter

项目摘要

DESCRIPTION (provided by applicant): Glia, which constitutes astrocytes and oligodendrocytes, are the most proliferative and abundant cell types in the central nervous system. Abnormal development of astrocytes and oligodendrocytes is associated with a number of neurological diseases and disorders such as amyolateral sclerosis (ALS), multiple sclerosis (MS), autism, epilepsy, schizophrenia, and glioblastoma, the deadliest of brain cancers. The basic-helix-loop-helix (bHLH) transcription factors Ascl1 and Olig2 are crucial for the specification and development of both astrocytes and oligodendrocytes, and are highly expressed in glioblastoma. The proposed project aims to: 1) determine the role and function of Ascl1 and Olig2 in regulating the generation of astrocytes and oligodendrocytes in the gray matter and white matter in the spinal cord; 2) determine the in vivo requirement of Ascl1 and Olig2 in brain tumors of a mouse model of glioblastoma; and 3) utilize Next-Generation sequencing techniques to identify on a genome-wide scale the DNA-binding profiles and direct transcriptional target genes of Ascl1 and Olig2 in glial progenitors in comparison to tumor cells of the glioblastoma mouse model. The culmination of this study will lead to new insights on the genetic regulatory networks of glial heterogeneity and glioblastoma development in the central nervous system.

描述（由适用提供）：构成星形胶质细胞和少突胶质细胞的神经胶质是中枢神经系统中最大的和丰富的细胞类型。星形胶质细胞和少突胶质细胞的异常发育与多种神经系统疾病和疾病有关，例如甲状腺外侧硬化症（ALS），多发性硬化症（MS），自闭症，癫痫，精神分裂症，精神分裂症和胶质母细胞瘤，是脑罐头癌症的最dencers虫。基本螺旋 - 环螺旋（BHLH）转录因子ASCL1和OLIG2对于星形胶质细胞和少突胶质细胞的规范和发展至关重要，并且在胶质母细胞瘤中高度表达。拟议的项目的目的是：1）确定ASCL1和Olig2在确定灰质和脊髓中白质中星形胶质细胞和少突胶质细胞的产生中的作用和功能； 2）确定胶质母细胞瘤小鼠模型的脑肿瘤中ASCL1和Olig2的体内需求；和3）与胶质母细胞瘤小鼠模型的肿瘤细胞相比，利用下一代测序技术在全基因组范围内识别ASCL1和Olig2的DNA结合谱和直接的转录靶基因。这项研究的高潮将导致对中枢神经系统中神经胶质异质性和胶质母细胞瘤发育的遗传调节网络的新见解。