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Role of cell cycle regulators in differentiation

细胞周期调节因子在分化中的作用

基本信息

批准号：
8319125
负责人：
Patrizia Casaccia
金额：
$ 37.08万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-15 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8319125
关键词：
Affect Binding Cancer Biology Cell Cycle Cell Cycle Proteins Cell Differentiation process Cells ChIP-seq Chromatin Chromatin Structure Co-Immunoprecipitations Collaborations Complex Data Deacetylation Development Discipline Dominant-Negative Mutation Down-Regulation E2F1 gene Energy Metabolism Enzymes Family Family member Funding Gene Cluster Gene Expression Gene Expression Profile Gene Targeting Genes Genetic Glioblastoma Grant HDAC1 gene Histone Acetylation Histones In Vitro Internal Ribosome Entry Site Kinetics Knowledge Link Malignant Neoplasms Mediating Metabolic Modeling Molecular Mus Nodal Oligodendroglia Oncogenes Pathology Physical condensation Physiological Proliferating Proteins Regulator Genes Role Shapes Sorting - Cell Movement Specificity Stem cells Testing Time Transcriptional Regulation Up-Regulation Validation c-Myc Staining Method cancer cell cdc Genes chromatin immunoprecipitation developmental neurobiology gene repression histone acetyltransferase in vivo interest member metaplastic cell transformation mouse model myelination nervous system disorder neuro-oncology neurodevelopment novel novel therapeutics nuclear reprogramming oligodendrocyte lineage prevent progenitor programs repaired

项目摘要

DESCRIPTION (provided by applicant): Our lab has identified an interesting relation between members of the Myc and E2f family of cell cycle regulators and chromatin changes and transcriptional regulation of differentiation of oligodendrocyte progenitors. We now propose to use primary cultures and genetic mouse models to test a new mechanistic model of oligodendrocyte differentiation. The results from the proposed experimental plan are likely to advance our knowledge not only in neural development and repair, but also in cancer and nuclear reprogramming and have wide implications for the development of novel therapeutic strategies. PUBLIC HEALTH RELEVANCE: The relationship between cell cycle and differentiation in progenitor cells is critical for a vast number of pathologies, ranging from cancer to repair. Although considerable progress has been made in the study of oncogenes in cellular transformation, still very little is known about their role in physiological conditions. This projet defines the role of Myc and E2F in the oligodendrocyte lineage and proposes a novel model of progenitor differentiation, linking cell cycle exit to chromatin condensation and transcriptional modulation.

描述（由申请人提供）：我们的实验室已经确定了细胞周期调节因子Myc和E2f家族成员与少突胶质细胞祖细胞分化的染色质变化和转录调节之间的有趣关系。我们现在建议使用原代培养和遗传小鼠模型来测试少突胶质细胞分化的新机制模型。从拟议的实验计划的结果可能会推进我们的知识，不仅在神经发育和修复，而且在癌症和核重编程和新的治疗策略的发展具有广泛的意义。公共卫生相关性：细胞周期和祖细胞分化之间的关系对于从癌症到修复的大量病理学是至关重要的。虽然癌基因在细胞转化中的研究已经取得了相当大的进展，但对它们在生理条件下的作用仍然知之甚少。该项目定义了Myc和E2F在少突胶质细胞谱系中的作用，并提出了一种新的祖细胞分化模型，将细胞周期退出与染色质凝聚和转录调节联系起来。