Molecular Mechanism of Transdifferentiation in the Pigmented Epithelial Cell

基于对蝾螈Wolffian晶状体再生的研究，我们研究了色素上皮细胞（PECs）向晶状体细胞转分化过程的分子调控机制。以下是1987年至1989年这三年的调查结果。(1)通过我们实验室开发的细胞培养程序的应用证明，从完全发育的人眼分离的PECs很容易转化为晶状体表型，就像在鸡胚PECs中观察到的那样。此外，我们成功地从去分化的人类PECs中分离出永久细胞系，并为研究人类细胞转分化的细胞和分子机制奠定了独特的体外细胞培养体系的基础。(2)完整地描述了鸡胚PECs晶状体转分化过程中色素细胞特异性基因和晶状体细胞特异性基因的表达模式。研究还表明，这些细胞类型特异性基因的表达在多能去分化PECs的再分化过程中受到转录调控。(3)从鸡胚PECs中分离到两个不同的基因。从结构分析的结果推测，这两个基因编码一种负责调节PECs去分化和转分化的蛋白质。(4)我们发现了一种细胞表面糖蛋白，它能原位稳定蝾螈PECs的分化状态。虽然这种糖蛋白不是PECs所特有的，但在中胚层组织和一些外胚层上皮中广泛存在，这种细胞表面分子在蝾螈晶状体再生过程中虹膜PECs的去分化中起着至关重要的作用。

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.