THE ADIPOSE CONVERSION OF 3T3 CELLS

3T3 细胞的脂肪转化

• 批准号: 3230222
• 负责人: HOWARD GREEN
• 金额: $ 22.6万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-03-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230222
• 关键词: adipocytes; adipose tissue; cell differentiation; chromatin; collagen; cyclic AMP; enzyme mechanism; fibroblasts; gene expression; genetic library; genetic mapping; genetic transcription; high performance liquid chromatography; isozymes; laboratory mouse; laboratory rat; lipid biosynthesis; messenger RNA; molecular cloning; nucleic acid probes; nucleic acid sequence; nucleosomes; protein biosynthesis; protein structure; radiotracer; regulatory gene; tissue /cell culture

When preadipose 3T3 cells arrest their growth and interact with an external adipogenic factor, they begin to convert to adipose cells. This is a faithful model of the formation of adipose cells in early developement. In the process of adipose conversion there is an extensive revision of the protein composition of the cytoplasm; this is necessary in order to provide the lipogenic and lipolytic enzymes and accesssory proteins for performance of the differentiated functions of the cell type. Using cDNA clones and ultimately genomic clones for some of the proteins participating in the differentiation, we will study the integrated or programmatic aspects of the adipose conversion, in order to learn how the cell coordinates the expression of this group of genes. Studies of transcription and mRNA formation in preadipose 3T3 cells, in converted 3T3 adipose cells and in cells of another 3T3 line unable to undergo conversion in response to adipogenic factor will enable us to define the order in which the genes respond. In particular, we will perform a kinetic analysis of these events during the course of adipose conversion. The relation of the order of expression of these genes to changes in chromatin structure will be explored. The expression of these genes will be studied in other tissues, such as liver and brain, whose program of differentiation overlaps the program in adipose differentiation. In this way we hope to learn how the expression of a given gene can be integrated into different programs in different cell types. These studies permit an approach to the study of obesity using cultured cells. Analysis of the molecular and cellular changes necessary for the formation of adipose cells from their precursors may be expected to shed light on the genesis of hyperplastic obesity.

当前脂肪 3T3 细胞停止生长并与外部相互作用时 脂肪形成因子，它们开始转化为脂肪细胞。 这是一个 早期发育中脂肪细胞形成的忠实模型。 在 脂肪转化的过程有一个广泛的修订 细胞质的蛋白质组成；这是必要的，以便提供 脂肪生成酶和脂肪分解酶以及辅助蛋白以提高性能 细胞类型的分化功能。 使用 cDNA 克隆和 最终，一些参与该过程的蛋白质的基因组克隆 差异化，我们将研究集成或程序化方面 脂肪转化，以了解细胞如何协调 这组基因的表达。 转录和 mRNA 研究 前脂肪 3T3 细胞、转化的 3T3 脂肪细胞和 另一个 3T3 系的细胞无法响应转化 脂肪形成因子将使我们能够定义基因的顺序 回应。 特别是，我们将对这些事件进行动力学分析 在脂肪转化过程中。 的顺序关系为 这些基因的表达会导致染色质结构的变化 探索过。 这些基因的表达将在其他组织中进行研究， 例如肝脏和大脑，其分化程序与 脂肪分化计划。 通过这种方式，我们希望了解如何 给定基因的表达可以整合到不同的程序中 不同的细胞类型。 这些研究提供了一种利用培养物来研究肥胖的方法 细胞。 分析必要的分子和细胞变化 由其前体细胞形成的脂肪细胞可能会脱落 阐明增生性肥胖的起源。