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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃祥博(Hsiang-Po Huang) | |
| dc.contributor.author | Yu-Feng Chien | en |
| dc.contributor.author | 簡裕峰 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:52:39Z | - |
| dc.date.available | 2025-08-01 | |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-10 | |
| dc.identifier.citation | [1] Zuo K, Qi Y, Yuan C, Jiang L, Xu P, Hu J, et al. Specifically targeting cancer proliferation and metastasis processes: the development of matriptase inhibitors. Cancer metastasis reviews 2019;38:507-24. [2] Sechler M, Borowicz S, Van Scoyk M, Avasarala S, Zerayesus S, Edwards MG, et al. Novel Role for gamma-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1). The Journal of biological chemistry 2015;290:15610-20. [3] Lin CY, Tseng IC, Chou FP, Su SF, Chen YW, Johnson MD, et al. Zymogen activation, inhibition, and ectodomain shedding of matriptase. Frontiers in bioscience : a journal and virtual library 2008;13:621-35. [4] Huang HP, Chang MH, Chen YT, Hsu HY, Chiang CL, Cheng TS, et al. Persistent elevation of hepatocyte growth factor activator inhibitors in cholangiopathies affects liver fibrosis and differentiation. Hepatology (Baltimore, Md) 2012;55:161-72. [5] Koivuniemi R, Makela J, Hokkanen ME, Bruelle C, Ho TH, Ola R, et al. Hepatocyte growth factor activator inhibitor-1 is induced by bone morphogenetic proteins and regulates proliferation and cell fate of neural progenitor cells. PloS one 2013;8:e56117. [6] Wu CJ, Feng X, Lu M, Morimura S, Udey MC. Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis. The Journal of clinical investigation 2017;127:623-34. [7] Ng VY, Ang SN, Chan JX, Choo AB. Characterization of epithelial cell adhesion molecule as a surface marker on undifferentiated human embryonic stem cells. Stem cells (Dayton, Ohio) 2010;28:29-35. [8] Cheng H, Fukushima T, Takahashi N, Tanaka H, Kataoka H. Hepatocyte growth factor activator inhibitor type 1 regulates epithelial to mesenchymal transition through membrane-bound serine proteinases. Cancer research 2009;69:1828-35. [9] Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. The Journal of clinical investigation 2009;119:1438-49. [10] Rangel MC, Karasawa H, Castro NP, Nagaoka T, Salomon DS, Bianco C. Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer. The American journal of pathology 2012;180:2188-200. [11] Allison TF, Powles-Glover NS, Biga V, Andrews PW, Barbaric I. Human pluripotent stem cells as tools for high-throughput and high-content screening in drug discovery. International Journal of High Throughput Screening 2015;5:1-13. [12] Tan JY, Sriram G, Rufaihah AJ, Neoh KG, Cao T. Efficient derivation of lateral plate and paraxial mesoderm subtypes from human embryonic stem cells through GSKi-mediated differentiation. Stem cells and development 2013;22:1893-906. [13] Evseenko D, Zhu Y, Schenke-Layland K, Kuo J, Latour B, Ge S, et al. Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 2010;107:13742-7. [14] Lee MS, Tseng IC, Wang Y, Kiyomiya K, Johnson MD, Dickson RB, et al. Autoactivation of matriptase in vitro: requirement for biomembrane and LDL receptor domain. American journal of physiology Cell physiology 2007;293:C95-105. [15] Wu CJ, Mannan P, Lu M, Udey MC. Epithelial cell adhesion molecule (EpCAM) regulates claudin dynamics and tight junctions. The Journal of biological chemistry 2013;288:12253-68. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78353 | - |
| dc.description.abstract | 在過去的許多文獻中都指出，SPI-1和SPx在癌細胞的epithelial-to-mesenchymal transition (EMT) 中扮演相當重要的角色。然而EMT並不是癌細胞特有的能力，在發育過程中，EMT和MET的功能更為複雜，對於許多組織的發育擁有舉足輕重的地位，但SPI-1和SPx在發育中的影響卻仍不清楚。因此本研究證明SPI-1和SPx在ESC和iPSC中皆有高度的表達，並且在經過發育中最早的EMT (中胚層分化) 之後，SPI-1和SPx皆有顯著的下降。更進一步而言，透過knockdown的研究後發現，SPI-1和SPx下降所造成的影響效果非常不穩定，因此在更詳細的了解分化的過程後，發現SPx可能在分化中有關鍵性的作用，該作用可能包含切割EpCAM來影響分化，而SPI-1具有調節SPx的功能，因此在分化中理當不可或缺，然而更詳細的作用機制仍需待未來進一步探討。 | zh_TW |
| dc.description.abstract | SPI-1 (serine protease inhibitor 1) and SPx (serine protease x) are reported to play important roles in epithelial-to-mesenchymal transition (EMT) of cancer cells in many studies. However, the function of SPI-1 and SPx does not well study in development currently even if the EMT and MET are also critical in fetus formation. In this study, we performed immunostaining and confocal microscopy of SPI-1 and SPx in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) during mesoderm differentiation which the first EMT function in development. We found that a lot of SPI-1 and few SPx distribute on the membrane of stem cells but SPI-1 and SPx decrease after mesoderm differentiation. However, in our current research results, we find SPx may interact with EpCAM on the cell membrane and affect mesoderm differentiation. The more precise function of the serine protease in mesoderm differentiation should be confirmed in the future study. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:52:39Z (GMT). No. of bitstreams: 1 U0001-2707202017075800.pdf: 6391500 bytes, checksum: 3d03e37556f516867822d9b98a389e88 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝 i 中文摘要 ii 英文摘要 iii 目錄 iv 圖表目錄 vii 第一章 前言 1 第二章 背景 2 I. SPI-1和SPx的生理作用 II. SPI-1和SPx在細胞分化上的作用 III. SPI-1和SPx在EMT中的功能 IV. 體外中胚層分化 第三章 研究目標 8 I. 確認SPI-1和SPx在pluripotent stem cells中的表達 II. 研究ESC和iPSC中胚層分化中SPI-1和SPx之變化 III. 透過knockdown SPI-1和SPx確認其功能 第四章 材料與方法 10 I. 細胞株和細胞培養 (cell lines and cell culture) II. 免疫螢光染色 (immunofluorescence staining) III. 中胚層分化 IV. 流式細胞儀分析 (flow cytometry) V. 定量型PCR (quantitative PCR, qPCR) VI. 西方墨點法 (western blotting) VII. shRNA knockdown VIII. siRNA knockdown 第五章 結果 15 I. SPI-1表現在ESC和iPSC的細胞膜上 II. SPx表現在ESC和iPSC的細胞膜和細胞質上 III. SPI-1和SPx皆在中胚層分化中降低 IV. SPI-1 knockdown和SPx knockdown對中胚層分化的影響 V. 中胚層分化第四天和第八天 VI. SPI-1 knockdown和SPx knockdown在分化8天的影響 VII. 利用siRNA knockdown SPI-1並進行第八天中胚層分化 VIII. 中胚層分化第四天和第八天之基因表現 IX. SPx和EpCAM在中胚層分化第四天結合在一起 X. SPI-1和SPx在分化中變化和功能的model 第六章 討論 26 第七章 結論 30 第八章 圖表 31 第九章 參考文獻 58 | |
| dc.language.iso | zh-TW | |
| dc.subject | 中胚層分化 | zh_TW |
| dc.subject | SPI-1 | zh_TW |
| dc.subject | SPx | zh_TW |
| dc.subject | EMT | zh_TW |
| dc.subject | EpCAM | zh_TW |
| dc.subject | EpCAM | en |
| dc.subject | mesoderm differentiation | en |
| dc.subject | SPx | en |
| dc.subject | SPI-1 | en |
| dc.subject | EMT | en |
| dc.title | 探討SPI-1和SPx在中胚層分化中之角色 | zh_TW |
| dc.title | The roles of SPI-1 and SPx in mesoderm differentiation of pluripotent stem cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李明學(Ming-Hsueh Li),張以承(Yi-Cheng Chang) | |
| dc.subject.keyword | SPI-1,SPx,EMT,中胚層分化,EpCAM, | zh_TW |
| dc.subject.keyword | SPI-1,SPx,EMT,mesoderm differentiation,EpCAM, | en |
| dc.relation.page | 59 | |
| dc.identifier.doi | 10.6342/NTU202001922 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 基因體暨蛋白體醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-08-01 | - |
| 顯示於系所單位： | 基因體暨蛋白體醫學研究所 | |
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