Grant-in-Aid for Scientific Research on Priority Areas
|Allocation Type||Single-year Grants |
|Research Institution||The Institute of Physical and Chemical Research (2003-2004)|
Kyoto University (2000-2002)
NISHIKAWA Shun-Ichi The institute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Group Director, 幹細胞研究グループ, グループディレクター (60127115)
ERA Takumi The Institute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (00273706)
OSAWA Masatake The lnstitute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (10344029)
UEMURA Akiyoshi The Institute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (30373278)
TOGAWA Atsushi The lnstitute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (30359799)
藤本 哲広 京都大学, 医学研究科, 教授
山下 潤 京都大学, 医学研究科, 助教授 (50335288)
吉田 尚弘 京都大学, 医学研究科, 助手 (20281090)
小川 峰太郎 京都大学, 医学研究科, 助教授 (70194454)
|Project Period (FY)
2000 – 2004
Completed (Fiscal Year 2004)
|Budget Amount *help
¥304,900,000 (Direct Cost: ¥304,900,000)
Fiscal Year 2004: ¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 2003: ¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 2002: ¥89,500,000 (Direct Cost: ¥89,500,000)
Fiscal Year 2001: ¥89,000,000 (Direct Cost: ¥89,000,000)
Fiscal Year 2000: ¥86,400,000 (Direct Cost: ¥86,400,000)
|Keywords||ES cell / endothelial cell / stem cell / mesoderm / melanocyte / bulge region / mesenchymal stem cell / DNA microarray / 分化誘導 / 色素細胞幹細胞維持機構 / 血管リモデリング分子機構 / 血管新生 / ガン周囲組織 / 血液細胞 / 抹消リンパ組織 / 血管分化 / 血液分化 / DNAアレー / パイエル板 / ガンの血管新生 / Ang 1 / VEGF / リンパ節 / 血管内皮 / 血液 / 平滑筋 / 間質細胞 / がん周囲組織 / VEGFR|
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
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