| 研究生: |
陳育瑞 Chen, Yu-Reui |
|---|---|
| 論文名稱: |
使人類誘導型多潛能幹細胞分化成血管內皮細胞之起始驅動因子 Essential drivers for the differentiation of endothelial cells from human induced pluripotent stem cells |
| 指導教授: |
江伯敏
Chiang, Po-Min |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 臨床醫學研究所 Institute of Clinical Medicine |
| 論文出版年: | 2014 |
| 畢業學年度: | 102 |
| 語文別: | 中文 |
| 論文頁數: | 70 |
| 中文關鍵詞: | iPS 細胞 、血管內皮細胞 、分化 、訊號刺激 |
| 外文關鍵詞: | iPS, endothelial cells, differentiate, essential signal |
| 相關次數: | 點閱:102 下載:0 |
| 分享至: |
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血管內皮細胞不論是在組織的修復跟器官的重組都扮演著很重要的生理
功能,但是如何利用簡單又有效的方法去得到從iPS 細胞分化而來的血管內皮
細胞卻仍未知,因此我們想要嘗試去建造一個能讓iPS 細胞分化成為血管內皮
細胞的完整系統,並利用這個系統去解釋是哪些訊號的刺激去控制整個血管內
皮細胞的分化。
而我們發現,血管前驅細胞跟成熟血管細胞可以在完整定義的系統下,藉
由人工化合物以及重組蛋白的刺激而有效的形成。另外,BMP4 在從血管前驅
細胞分化為血管內皮細胞的形成上是必需的細胞激素。透過利用shRNA
knockdown 特定的基因之後,我們發現在血管前驅細胞分化為血管內皮細胞過
程中,無論是細胞或是細胞表面之間都需要特定的分子或媒介來完成這個過程,
而這個過程也都與BMP4 的訊息傳遞路徑有所關聯。
具有使血管內皮細胞高效率分化且不需要任何含動物成分的系統讓我們
對於臨床治療的領域又往前邁一大步。除此之外,透過我們所定義的系統來調
控單一因子,我們可以證明並解釋在從血管前驅細胞分化成為血管內皮細胞的
過程裡,驅使整個分化主要的核心系統為何。
It is important to develop a way to obtain endothelial cells from induced
pluripotent stem (iPS) cells. The endothelial cells can be used for tissue repair,
organ engineering and biological characterizations. However, an efficient and clean
method to obtain endothelial cells from induced pluripotent stem (iPS) cells is still
absent. Here we tried to develop a defined system to differentiate iPS cells into
endothelial cells and use the system to further elucidate the signals essential for the
formation of endothelial cells.
We found endothelial precursors and mature endothelial cells can be derived
efficiently in the defined system composed of only synthetic chemicals and
recombinant proteins. Further, BMP4 is the essential trigger for the formation of
endothelial cells from hemangioblasts. By knocking down gene expression with
shRNA, we demonstrated a specific and selective set of intracellular and
cell-surface mediators required for the hemangioblasts-to-endothelium transition.
The high-efficiency derivation of endothelial cells by the defined system
allows us to rapidly extend our finding to the therapeutics. Further, by manipulating
individual factors and mediators during differentiation, we demonstrate the potential
to decipher core programs driving the formation of endothelial cells in the near
future.
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校內:2024-12-31公開