Controlling the rate of adipocyte differentiation: Experiments and theory

控制脂肪细胞分化率：实验和理论

• 批准号: 8816954
• 负责人: Mary N Teruel
• 金额: $ 36.11万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8816954
• 关键词: Address; Adipocytes; Adult; Aging; Architecture; Bacteria; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cell Count; Cell Differentiation process; Cell Fraction; Cells; ChIP-seq; Computer Simulation; Data; Data Set; Defect; Diabetes Mellitus; Epidemic; Feedback; Genetic Transcription; Goals; Grant; Hematopoietic; Human; Insulin Resistance; Life; Lipids; Mammalian Cell; Mass Spectrum Analysis; Measures; Medical; Microscopy; Modeling; Molecular; Molecular Models; Neurons; Noise; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Organ Size; Organism; Outcome; Play; Population; Process; Proliferating; Proteins; Regulation; Role; Side; Source; Stable Populations; Stem cells; Stimulus; System; Testing; Therapeutic Intervention; Time; Tissues; Translations; Undifferentiated; Variant; Work; adipocyte differentiation; cell type; cellular imaging; chemical genetics; genome-wide; in vivo; lipid biosynthesis; mRNA Stability; models and simulation; molecular modeling; novel strategies; precursor cell; protein expression; public health relevance; research study; response; system architecture; theories; tool; transcriptome sequencing

DESCRIPTION (provided by applicant): Cell differentiation is a process in which a precursor cell develops into a new type of cell in response to specific internal or external stimuli. The lon term goal of this proposal is to understand how to control low rates of terminal cell differentiatin such are observed in vivo to maintain tissue size under normal conditions. Adipocyte differentiation, or the conversion of proliferating precursor cells into non-dividing fat cells or adipocytes capable of accumulating lipid, is one of the most accessible experimental systems for investigating terminal differentiation in mammalian cells. Understanding adipogenesis also has great medical relevance since defects in adipogenesis underlie the current worldwide epidemics in obesity, insulin resistance, diabetes, and cardiovascular disease. Computational modeling, quantitative mass spectrometry and single-cell microscopy will be used to identify and understand the system architecture and molecular mechanisms that cells use to have sufficient cell-to-cell variability in protein expression (noise) required to regulate small fractional rates f cell differentiation while at the same time allowing for controlled and stable terminal cell differentiation. The outcome of this work will be a fundamental understanding of the system architecture and molecular mechanisms that can control small fractional differentiation rates, opening up new venues of therapeutic intervention for the defective adipocyte differentiation underlying insulin resistance and type 2 diabetes. The results of this study will likely have broad relevance for all cell differentiation processes and may help in developing novel approaches to restore defective or aging cardiac, neuronal, hematopoietic, and other tissues.

描述（由申请人提供）：细胞分化是一个过程，在该过程中，前体细胞响应特定的内部或外部刺激而形成新型细胞。该提案的LON术语目标是了解如何在体内观察到如何控制低末端细胞分化的低率，以在正常条件下维持组织大小。脂肪细胞分化，或者将增殖的前体细胞转化为能够累积脂质的非分裂脂肪细胞或脂肪细胞，是研究哺乳动物细胞中末端分化的最易接收的实验系统之一。了解脂肪形成也具有很大的医学意义，因为脂肪形成的缺陷是肥胖，胰岛素抵抗，糖尿病和心血管疾病的当前全球流行病的基础。计算模型，定量质谱和单细胞显微镜将用于识别和了解细胞在蛋白质表达中具有足够的细胞对细胞变异性（噪声）来调节小分子速率F细胞差异所需的细胞对细胞变异性（噪声），而同时允许对受控的和稳定的终末分化。这项工作的结果将是对系统结构和分子机制的基本理解，这些机制可以控制小分离率，为胰岛素耐药性和2型糖尿病的脂肪细胞分化有缺陷的脂肪细胞分化打开了新的治疗干预场所。这项研究的结果可能很广 与所有细胞分化过程的相关性，并可能有助于开发新的方法，以恢复心脏，神经元，造血和其他组织的缺陷或衰老。