Production of cells that constitute microenvironment of cancer.

产生构成癌症微环境的细胞。

基本信息

批准号：
12219209
负责人：
NISHIKAWA Shun-Ichi
金额：
$ 195.14万
依托单位：
The Institute of Physical and Chemical Research (2003-2004)Kyoto University (2000-2002)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

项目摘要

1) We established a method to induce vascular components from ES cells that enables cellular analysis of normal endothelial and mural cells. Using this experimental system, we determine the role of Fik1, Fit1, and Flt4 in endothelial cells. Moreover, we have identified a culture condition to induce endothelial cells from human ES cells.2) We established a method to manipulate angiogenesis in the neonatal retina by intraocular injection of various reagents. Using this system, we have identified LIF and Tlx as molecules regulating astrocyte-endothelial intereactions, and PDGFRβ, Ang1, and Plexin D1 as molecules involved in interaction between endothelial cells and mural cells.3) Using a culture system to induce ES cell differentiation to hematopoietic stem cells, we identify the stage when SCL, Runx1 and GATA1 are involved. While we succeeded to determine a defined culture condition to induce endothelial and hematopoietic cells from ES cells, we could not attain the goal to induce the de … More finitive hematopoietic stem cells from ES cells.4) We have established a defined condition that allows selective induction of the definitive endoderm and demonstrated presence of bipotent mesendoderm that can give rise to both definitive endoderm and mesoderm.5) Taking advantage of a data base that contains DNA microarray data of varying intermediate stages appearing in ES cell differentiation culture (this data base is a project of Kobe City), we tested a new method to isolate novel genes that are involved in various process of cell specification during embryogenesis. We have identified three novel molecules and proved that they are indeed play an essential role in embryogenesis.6) We determined that the stem cell compartment of melanocyte system locates in the bulge-region of hair follicles. Those melanocyte stem cells are picked up individually to make a stem cell specific library From the gene expression profile in this library, we found that the stem cell compartment is characterized by its low expression of house keeping genes. We also found that the stem cell expresses a high level of 1) Wnt inhibitors, 2) Notch/Hes1, and 3) molecules that may potentially suppress basic transcriptional machinery. Among those characteristics, we investigated the role of Notch signaling in melanocyte, and demonstrated that Notch/Hes1 signaling is essential for melanocyte development and maintenance of the stem cell compartment.7) We demonstrated that a part of mesenchymal stem cells are derived from neuroepithelial cells. Less

1) 我们建立了一种从 ES 细胞诱导血管成分的方法，可以对正常内皮细胞和壁细胞进行细胞分析，使用该实验系统，我们确定了 Fik1、Fit1 和 Flt4 在内皮细胞中的作用。 2）我们建立了一种通过眼内注射各种试剂来操纵新生儿视网膜血管生成的方法，使用该系统，我们已经鉴定了LIF和LIF。 Tlx作为调节星形胶质细胞-内皮相互作用的分子，PDGFRβ、Ang1和Plexin D1作为参与内皮细胞和壁细胞之间相互作用的分子。3)使用培养系统诱导ES细胞分化为造血干细胞，我们确定了以下阶段：虽然我们成功确定了从 ES 细胞诱导内皮细胞和造血细胞的明确培养条件，但我们无法确定 SCL、Runx1 和 GATA1。达到从 ES 细胞中诱导去定形造血干细胞的目标。4) 我们已经建立了一个明确的条件，允许选择性诱导定形内胚层，并证明存在可以产生定形内胚层和中胚层的双能中内胚层。 5) 利用包含ES细胞分化培养中出现的不同中间阶段的DNA微阵列数据的数据库（该数据库是神户市的一个项目），我们测试了一种分离新基因的新方法我们已经鉴定出三种新分子，并证明它们确实在胚胎发生过程中发挥着重要作用。6）我们确定黑素细胞系统的干细胞区室位于黑素细胞的凸起区域。毛囊中的黑素细胞干细胞被单独挑选出来，形成干细胞特异性文库。从该文库的基因表达谱中，我们发现干细胞区室的特点是管家基因的低表达。干细胞表达高水平的 1) Wnt 抑制剂、2) Notch/Hes1 和 3) 可能抑制基本转录机制的分子在这些特征中，我们研究了 Notch 信号传导在黑素细胞中的作用，并证明 Notch/Hes1 信号传导对于黑素细胞至关重要。黑素细胞的发育和干细胞区室的维持。7)我们证明部分间充质干细胞来源于神经上皮细胞。