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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林泰元(Thai-Yen Ling) | |
| dc.contributor.author | Tsung-Han Yu | en |
| dc.contributor.author | 余宗翰 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:31:57Z | - |
| dc.date.available | 2020-09-24 | |
| dc.date.copyright | 2015-09-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-13 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52877 | - |
| dc.description.abstract | 藉由先前發現的無血清培養原代培養系統，可以取得一群能形成細胞群聚、自我增生且具有分化成肺泡第一型表皮細胞能力的肺部前驅幹細胞 (mPSCs)，肺部前驅幹細胞會表現Oct-4、SSEA-1以及Sca-1這些代表細胞具有多能性之轉錄因子，同時還會表現柯薩奇病毒和腺病毒受體(CAR)，因此可藉由流式細胞儀將CAR陽性之細胞分選、純化。肺部前驅幹細胞在分化系統的培養環境下，最明顯的變化為肺泡第一型表皮細胞表面標誌的表現以及細胞型態的變化。但是分化的機轉能然未知。透過第三型乙型轉化生長因子(TGF-β3)基因剃除鼠的動物模型，觀察到發育不完全的肺泡、肺部前驅幹細胞不正常堆疊在支氣管壁上以及鮮少肺泡第一型表皮細胞表現。藉由基因剃除鼠模型的線索，我們利用肺部前驅幹細胞分化成肺泡第一型表皮細胞的分化模型，來探討肺部前驅幹細胞分化的機轉。實驗中觀察到，肺部前驅幹細胞在分化的過程中會分泌第三型乙型轉化生長因子，並且活化下游的分子Smad3。除此之外，轉錄因子Snail1的表現量會增加，並調控cdc42、rac-1以及細胞骨架相關蛋白的表現量，進而調控細胞型態之變化。因此推測第三型乙型轉化生長因子會驅動肺部前驅幹細胞的分化。 | zh_TW |
| dc.description.abstract | In previous study which published in 2006, reported a selective serum-free culture system for primary neonatal mice pulmonary cells. An special population cells, mPSCs, could be enriched through the culture system, which expresses the markers of stem cells, such as octamer-binding transcription factor-4 (Oct-4), stage specific embryonic antigen-1 (SSEA-1) and stem cell antigen-1 (Sca-1). The mPSCs are also coxsackievirus and adenovirus receptor (CAR) - positive. Therefore, the mPSCs could be purified by fluorescence-activated cell sorting (FACS). During the differentiation process, the surface marker of type-I pneumocyte and the morphology transforming were changed dramatically. But the mechanism was still unknown. Meanwhile, the transforming growth factor-beta 3 (TGF-β3) knockout mice model, the retard developing lung, the abnormal accumulation of CAR-positive cells and poor development of alveolar type-I pneumocytes, provided the clue of differentiation. Therefore, we used the model of mPSCs differentiation into alveolar type-I pneumocyte to study the biological function of TGF-β3 in the developing lung. The secreted TGF-β3 in the culture system was increased during differentiation and the downstream signaling molecular, Smad3, was activated. Further, the small G protein, cdc42 and rac-1, mediate the cytoskeleton remodeling via snail1 pathway. We supposed that the differentiation process of mPSCs to alveolar type-I pneumocytes was initiated by TGF-β3. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:31:57Z (GMT). No. of bitstreams: 1 ntu-104-R02443016-1.pdf: 3436087 bytes, checksum: 5c8ffed6abaef5c76b13dce8a3410d7a (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | Abbreviation list 3 Chapter 1 : Introduction 4 1.1 Stem/progenitor cells in the lung 5 1.2 The lung development stage of lung 6 1.3 Activation of TGF-β 7 1.4 The TGF-β signalings 11 1.5 Regulation of TGF-β in lung 12 1.6 Cell migration and cytoskeleton 15 1.7 Aim of study 17 Chapter 2 : Materials and Methods 18 2.1 Primary culture of mouse pulmonary stem/progenitor cells 19 2.2 mPSCs isolation 20 2.3 In vitro differentiation of mPSCs 20 2.4 Compounds for experiments 20 2.5 Antibodies 21 2.6 Immunohistochemistry 21 2.7 Immunocytochemistry 22 2.8 Real-time quantitative polymerase chain reaction (RT-QPCR) 23 2.9 Western blot 24 2.10 Enzyme-linked immunosorbent assay (ELISA) 24 Chapter 3 : Results 25 3.1 The lack of TGF-β3 caused the aberrant lung development 26 3.2 TGF-β3 knockout caused the alteration of cell population in alveolar 26 3.3 The gene expression profile and surface marker of normal differentiation and inhibitor treatment of mPSCs 27 3.4 The differentiation process of mPSCs is TGF-β3 dependent 28 3.5 The TGF-β3 triggers the differentiation process of mPSCs 29 3.6 The TGF-β3 mediated the differentiation process via Smad3 29 3.7 The small G protein regulated the morphology transforming 30 Chapter 4 : Discussion 31 4.1 Differentiation of alveolar type-I pneumocytes in vitro 32 4.2 The TGF-β signaling in the alveolarization 33 4.3 The morphology transforming of alveolar type-I pneumocytes 34 4.4 The potential mechanism of mPSCs differentiation into alveolar type-I like cells 34 Chapter 5 : Figures and legends 36 5.1 The lack of TGF-β3 caused the aberrant lung development 39 5.2 The TGF-β3 knockout caused the alteration of cell population in alveolar 41 5.3 The gene expression profile and surface marker of normal differentiation and inhibitor treatment of mPSCs 43 5.4 The differentiation process of mPSCs is TGF-β3 dependent 45 5.5 The TGF-β3 triggers the differentiation process of mPSCs 47 5.6 The TGF-β3 mediated the differentiation process via Smad3 49 5.7 The small G protein regulated the morphology transforming 52 Chapter 6 : References 53 | |
| dc.language.iso | en | |
| dc.subject | 前驅細胞 | zh_TW |
| dc.subject | 轉化生長因子 | zh_TW |
| dc.subject | 肺泡 | zh_TW |
| dc.subject | 發育 | zh_TW |
| dc.subject | alveolar | en |
| dc.subject | transforming growth factor | en |
| dc.subject | development | en |
| dc.subject | progenitor cell | en |
| dc.title | 第三型乙型轉化生長因子調控肺泡細胞發育機制之探討 | zh_TW |
| dc.title | The study for the mechanism of TGF-β3 regulation in the maturation of alveolar cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 江伯倫(Bor-Luen Chiang),曹伯年(Po-Nien Tsao),陳惠文(Huei-Wen Chen),何肇基(Chao-Chi Ho) | |
| dc.subject.keyword | 肺泡,前驅細胞,發育,轉化生長因子, | zh_TW |
| dc.subject.keyword | alveolar,progenitor cell,development,transforming growth factor, | en |
| dc.relation.page | 58 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-13 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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