Mechanisms controlling stabilization of differentiation and transdifferentiation in the animal tissue cell.

控制动物组织细胞分化和转分化稳定的机制。

基本信息

批准号：
04404004
负责人：
EGUCHI Goro
金额：
$ 10.24万
依托单位：
National Institute for Basic Biology
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

Through studies for three fiscal years from 1992 to 1994, the following results were obtained.1.A gene encoding TGFbeta-binding protein, which is expressed by chicken retinal pigmented epithelial cells (RPECs), produces 5.0kb and 6.0kb mRNAs by alternative splicing. The 5.0kb mRNA product is secreted and the 6.0kb mRNA product binds to extracellular matrix (ECM) of RPECs. Both products regulate the cell state and transdifferentiation of RPECs in vitro through modulating function of TGFbeta secreted by RPECs themselves. It has been also found that bFGF is one of major factors regulating RPECs in their expre-ssion of TGFbeta and its binding protein. In addition, a nobel serine-protease inhibitor has been found to be specifically expressed by RPECs and play essential roles in functional differentiation and maintenance of function of this cell type. 2. In addition to the fact that mature human RPECs can readily transdiffe-rentiate into lens cells when dissociated and cultured, it has been clealy demonstrated that a clonal cell line derived from 80-year-old human RPECs can express neurofilament protein submits to trans-differentiate into neuronal phenotypes. This result is the first evidence that the RPEC of even mature human can spontaneously transdifferentiate into neuronal cells under adequate conditions. 3. It has been found that the RPECs are very sensitive against cell culture condition, particularly serum added to the culture media. Through detailed comparison between RPECs and iris pigmented epithelial cells (IPECs) in culture, IPECs is much less sensitive and can be stably maintained in vitro. Based on this finding, much more powerful cell culture system of lens transdifferentiation has been established using one-day-old chicken IPECs. This system must contribute to future progress of our studies on transdifferentiation.

通过从1992年到1994年的三个财政年度的研究，获得了以下结果。1.A编码TGFBETA结合蛋白的基因，该基因由鸡肉视网膜色素上皮细胞（RPEC）表达，可通过替代的剪接产生5.0kb和6.0kb mRNA。 5.0kb mRNA产物分泌，6.0kb mRNA产物与RPEC的细胞外基质（ECM）结合。两种产品都通过RPEC本身分泌的TGFBETA的调节功能来调节RPEC在体外的细胞状态和转变。还发现，BFGF是调节RPEC在TGFBETA及其结合蛋白中调节RPEC的主要因素之一。此外，已经发现诺贝尔丝氨酸抑制剂是由RPEC特别表达的，并在该细胞类型功能的功能分化和维持中起着重要作用。 2。除了以下事实：当分离和培养时，成熟的人RPEC可以轻松地将其转化为晶状体细胞，也已经证明，从80年历史的人RPEC中得出的克隆细胞系可以表达神经丝的蛋白质蛋白可以将其提交到转化为神经元现象中。该结果是第一个证据表明，即使成熟的人的RPEC也可以在适当的条件下自发转变为神经元细胞。 3。已经发现，RPEC对细胞培养条件非常敏感，尤其是在培养基中添加的血清。通过培养中RPEC和虹膜有色上皮细胞（IPEC）之间的详细比较，IPEC敏感得多，并且可以在体外稳定地保持。基于这一发现，使用一日历史的鸡肉Ipec建立了更强大的晶状体转变细胞培养系统。该系统必须有助于我们对转变的研究的未来进步。