Molecular Mechanism of Transdifferentiation in the Pigmented Epithelial Cell

色素上皮细胞转分化的分子机制

基本信息

批准号：
62480020
负责人：
EGUCHI Goro
金额：
$ 3.58万
依托单位：
Okazaki National Research Institutes
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Based on studies of Wolffian lens regeneration in the newt, in which the lens can be regenerated from the iris pigmented epithelium, we have investigated molecular mechanisms regulating the processes of transdifferentiation of pigmented epithelial cells (PECs) to lens cells. The following findings have been established for three years from 1987 to 1989.(1) It has been proved by application of cell culture procedures developed in our laboratory that PECs dissociated from fully-grown human eyes readily transdifferentiate into lens phenotype in the manner observed in chick embryo PECs. In addition, we succeeded in isolation of permanent cell lines from dedifferentiated human PECs, and also in establishing the basis of a unique in vitro cell culture system which must be highly useful for studying cellular and molecular mechanisms of transdifferentiation in human cells.(2) We have completely described the pattern of expression of both pigment cell- and lens cell-specific genes in the whole sequence of lens transdifferentiation in chick embryo PECs. It has also shown that expression of these cell type-specific genes are transcriptionally regulated in the processes of reddiferentiation of multipotent dedifferentiated PECs.(3) Two different genes were isolated from chick embryo PECs. It has been assumed from the result of structural analyses that both genes code for a protein responsible for regulation of dedifferentiation and transdifferentiation of PECs.(4) We have found a cell surface glycoprotein which stabilize the differentiated state of PECs of the newt in situ. Although this glycoprotein is not specific to the PECs but widely detected in mesoderm-originated tissues and some of ectoderm-originated epithelia, this cell surface molecule plays an essential role in dedifferentiation of iris PECs in the process of lens regeneration in the newt.

基于对NEWT中的Wolffian晶状体再生的研究，其中可以从虹膜色素上皮细胞中再生晶状体，我们研究了调节色素上皮细胞（PEC）对镜片细胞转变过程的分子机制。从1987年到1989年已经建立了三年的发现。（1）通过在我们的实验室中开发的细胞培养程序证明，PEC与完全生长的人眼分离的人眼很容易以在雏鸡PEC中观察到的方式将其转变为镜头表型。 In addition, we succeeded in isolation of permanent cell lines from dedifferentiated human PECs, and also in establishing the basis of a unique in vitro cell culture system which must be highly useful for studying cellular and molecular mechanisms of transdifferentiation in human cells.(2) We have completely described the pattern of expression of both pigment cell- and lens cell-specific genes in the whole sequence of lens transdifferentiation in chick embryo PECs.它还表明，这些细胞类型特异性基因的表达在多蛋白去分化的PEC的红相介质过程中受到转录调节。（3）从雏鸡的胚胎PEC中分离出两个不同的基因。从结构分析的结果中可以假设，这两个基因都代码用于调节PEC的蛋白质的蛋白质。尽管该糖蛋白不是针对PEC的特异性，而是在中胚层填充的组织和某些外胚层原始的上皮菌中被广泛检测到的，但该细胞表面分子在纽特透镜再生过程中iris PEC过程中的去分化中起着至关重要的作用。