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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，该方法能够对正常内皮细胞和壁细胞进行细胞分析。使用这个实验系统，我们确定Fik 1，FIT 1和Flt 4在内皮细胞中的作用。此外，我们已经确定了一种培养条件，以诱导内皮细胞从人ES细胞。2）我们建立了一种方法来操纵新生儿视网膜血管生成的眼内注射的各种试剂。利用该系统，我们鉴定了LIF和Tlx是调节星形胶质细胞-内皮细胞相互作用的分子，PDGFRβ、Ang 1和Plexin D1是参与内皮细胞和壁细胞相互作用的分子。3）利用培养系统诱导ES细胞分化为造血干细胞，我们鉴定了SCL、Runx 1和GATA 1参与的阶段。虽然我们成功地确定了一个确定的培养条件，从ES细胞诱导内皮细胞和造血细胞，但我们不能达到诱导内皮细胞和造血细胞的目的。 ...更多信息 4）我们已经建立了一个确定的条件，该条件允许选择性诱导定形内胚层，并证明了双能中内胚层的存在，该中内胚层可以产生定形内胚层和中胚层。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（该数据库是科比市的一个项目），我们测试了一种分离新基因的新方法，所述新基因涉及胚胎发生期间细胞特化的各种过程。我们已经鉴定了三个新的分子，并证明它们确实在胚胎发生中起重要作用。6）我们确定黑素细胞系统的干细胞区室位于毛囊的隆起区域。这些黑素细胞干细胞被单独挑选，以制备干细胞特异性文库。从该文库的基因表达谱中，我们发现干细胞区室的特征在于其低表达的管家基因。我们还发现干细胞表达高水平的1）Wnt抑制剂，2）Notch/Hes 1，和3）可能潜在抑制基本转录机制的分子。在这些特征中，我们研究了Notch信号在黑素细胞中的作用，并证明Notch/Hes 1信号对黑素细胞的发育和干细胞区室的维持是必不可少的。7）我们证明了部分间充质干细胞来源于神经上皮细胞。少