TERMINAL DIFFERENTIATION OF EPIDERMAL AND ADIPOSE CELLS

表皮细胞和脂肪细胞的终末分化

• 批准号: 3479272
• 负责人: HOWARD GREEN
• 金额: $ 82.15万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3479272
• 关键词: adipocytes; cell differentiation; cell growth regulation; complementary DNA; crosslink; glycerol 3 phosphate dehydrogenase; growth factor; human tissue; keratin; keratinocyte; laboratory mouse; laboratory rat; membrane proteins; messenger RNA; molecular cloning; nucleic acid sequence; protein biosynthesis; retinoids; skin; skin neoplasms; somatotropin; tissue /cell culture

This work is devoted to the study under simple culture conditions of two differentiating mammalian cell types: 1) the human epidermal cell and its close relatives the keratinocytes of other stratified squamous epithelia; this cell type undergoes a program of terminal differentiation to produce a final stage resembling the corneocyte and 2) a preadipose cell line derived from 3T3 and able to differentiate terminally into adipocytes. For both systems we have a number of proteins that are characteristic of the cell in its terminally differentiated state, together with corresponding cDNA and genomic clones. We plan to examine the transition from precursor state, in which the cells are capable of either long term proliferation (human keratinocyte) or indefinite proliferation (3T3 preadipocyte), to a terminally differentiated state in which further division is impossible. We will examine the appearance of specific markers of differentiation in order to understand how the program of differentiation is coordinated. For the epidermal cell we will use cDNA and genomic clones for involucrin and several of the keratins; for adipose differentiation similar clones for glycerophosphate dehydrogenase and two unidentified marker proteins of 13 and 28 kd. This study will include an analysis of the structure of the corresponding genes, the effects of vitamin A on the differentiation of cultured epidermal cells (the regulation of keratin synthesis and of envelope cross-linking), and the effects of growth hormone in promoting the differentiation of preadipose cells. We will attempt to identify the properties of the colony forming epidermal cell, and the alteration of these properties in neoplastic keratinocytes. We will examine the possible role of IGF-1 (the growth hormone induced polypeptide) on clonal expansion of young differentiating adipose cells. These studies are expected to shed light on how differentiation normally leads to the arrest of cell mutiplication and how loss of this coupling leads to neoplasia.

本研究在两种不同的培养基中， 区分哺乳动物细胞类型：1）人表皮细胞及其 与其他复层鳞状上皮的角质形成细胞关系密切; 这种细胞类型经历终末分化程序， 最终阶段类似于角质细胞和2）前脂肪细胞系来源 来自3 T3并且能够终末分化为脂肪细胞。 为 我们有许多蛋白质是细胞的特征， 其终末分化状态，连同相应的cDNA， 基因克隆 我们计划研究从前体状态的转变，在这种状态下， 能够长期增殖（人角质形成细胞）或 无限期增殖（3 T3前脂肪细胞），至终末分化 不可能进一步分裂的状态。 我们会研究 出现特异性分化标志物，以便了解 差异化的程序是如何协调的 对于表皮细胞 我们将使用cDNA和基因组克隆的外皮蛋白和几个 角蛋白;对于脂肪分化，甘油磷酸盐的类似克隆 脱氢酶和两种未鉴定的13和28 kd标记蛋白。 这 研究将包括分析相应基因的结构， 维生素A对体外培养表皮细胞分化的影响 (the角蛋白合成和包膜交联的调节），以及 生长激素促进人胚肺细胞分化的作用 前脂肪细胞 我们将尝试识别殖民地的属性 形成表皮细胞，以及这些性质的改变， 肿瘤性角质形成细胞。 我们将研究IGF-1的可能作用（ 生长激素诱导多肽）对幼兔克隆扩增的影响 分化脂肪细胞。 这些研究有望揭示 分化通常如何导致细胞增殖的停滞， 这种结合的缺失是如何导致肿瘤形成的