TERMINAL DIFFERENTIATION OF EPIDERMAL AND ADIPOSE CELLS

该实验室致力于研究人类角质形成细胞， 增殖、终末分化及其特异基因 表情 角质形成细胞是一个独特的例子， 分化细胞类型，对肿瘤变化高度敏感。 因为这种细胞类型现在可以有效地培养， 由于细胞在培养中的分化特性，大多数工作使用细胞培养物。 然而，培养物可容易地移植到无胸腺动物， 它们生成正常的人类表皮。 这是一个非常敏感的测试， 正常角质形成细胞;用病毒转化培养的细胞 癌基因的结果非常明显的干扰分化的 移植上皮的结构。 没有其他组织可以 很容易从培养的细胞中产生，并以这种方式进行研究。 大部分的工作将集中在调控基因表达，使用 外皮蛋白和其他终末分化的特殊蛋白质。在 这项工作，研究转染的基因及其在细胞中的表达， 小（增殖）和大（终末分化）细胞， 通过淘洗分离，已经表明基因表达与 组织和细胞隔室特异性。 基因表达的变化 将研究培养细胞的移植。 启动基因的信号 在大细胞中的表达必须与那些阻止 增殖，因为改变基因表达是发展的基础， 肿瘤形成

This laboratory is devoted to the study of the human keratinocyte; its multiplication, its terminal differentiation, and its specific gene expression. The keratinocyte is a unique example of a terminally differentiating cell type with high susceptibility to neoplastic change. Because the cell type is now so efficiently cultivable and exhibits many differentiated properties in culture, most of the work uses cell cultures. However, the cultures are readily transplantable to athymic animals where they generate normal human epidermis. This is a very sensitive test for normal keratinocytes; transformation of the cultured cells with a viral oncogene results in very evident perturbation of the differentiated structure of the grafted epithelium. There is no other tissue which can be easily generated from cultured cells and studied this way. Much of the work will be focused on regulated gene expression, using involucrin and other specialized proteins of terminal differentiation. In this work, study of transfected genes and their resulting expression in small (proliferating) and large (terminally differentiating) cells, separated by elutriation, has already shown that genes are expressed with tissue and cell compartment specificity. Changes in gene expression after grafting of cultured cells will be studied. The signals that turn on gene expression in large cells must be closely related to those that arrest proliferation, since altered gene expression is basic to the development of neoplasia.