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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄭永銘 | zh_TW |
dc.contributor.advisor | Yung-Ming Jeng | en |
dc.contributor.author | 李嘉涵 | zh_TW |
dc.contributor.author | Chia-Han Lee | en |
dc.date.accessioned | 2021-07-11T14:34:34Z | - |
dc.date.available | 2024-02-28 | - |
dc.date.copyright | 2018-10-09 | - |
dc.date.issued | 2018 | - |
dc.date.submitted | 2002-01-01 | - |
dc.identifier.citation | 1. Reference
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77773 | - |
dc.description.abstract | 表觀遺傳學在很多生物現象扮演重要角色,包括癌症生成和細胞分化。Ten eleven translocation (TET) 蛋白是一群染色質重塑因子,經由胞嘧啶的羥甲基化(5-hydroxymethelation of cytosine)參與在DNA去甲基化的過程中。我們以免疫染色法發現在多種肉瘤,5-hydroxymethylcytosine (5-hmC)有減少的現象。其中,分化良好型脂肪肉瘤5-hmC沒有減少而去分化型脂肪肉瘤的5-hmC常見減少。因此,我們認為胞嘧啶的羥甲基化可能和脂肪細胞的分化有關。 在3T3L1細胞株的實驗中,我們發現脂肪細胞分化的過程中,TET1和5-hmC的表現會提升。且沈默掉TET1基因會阻饒脂肪細胞的分化。利用即時聚合酶鏈鎖反應,我們發現CEBPα是TET1可能的下游目標基因,並且發現TET1經由控制CKIs調節脂肪分化。我們的結果顯示TET1的調控對於脂肪形成的過程中是重要的,而且調控CEBPα的表現量為其可能的原因。 | zh_TW |
dc.description.abstract | Epigenetic changes play important roles in many biological phenomena including cancer development and cell differentiation. Ten eleven translocation (TET) proteins are a group of chromatin remodeling factors involved in the demethylation of DNA via 5-hydroxymethelation of cytosine. We found that the 5-hydroxymethelation (5-hmC) decreased in many types of sarcoma by immunohistochemistry. Especially, we discovered that 5-hmC levels were preserved in well-differentiated liposarcoma and lost in dedifferentiated liposarcoma. Therefore, we hypothesized that methylation of cytosine may be related to the differentiation of adipocyte. In the experiment using 3T3-L1 cells, we found that the expression of TET1 and the level of 5-hmC increased during differentiation. Silence of TET1 gene blocked the differentiation of adipocyte. We used real-time PCR assay found that CEBPα may be downstream targets of TET1, and TET1 regulated adipocytic differentiation through CKIs. Our results show that the regulation of TET1 is important for adipogenesis and probably through the target gene CEBPα. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:34:34Z (GMT). No. of bitstreams: 1 ntu-107-R05444001-1.pdf: 9722475 bytes, checksum: 58f6324f5518cd72f7b8e97e8eb989c7 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | Contents
口試委員會審定書會審定書 I 謝辭 II 中文摘要 III Abstract IV Contents V 1. Introduction 1 1.1. Sarcoma 1 1.2. Genetic change of sarcoma 2 1.3. Histopathology and genetic of liposarcoma 3 1.4. Adipocyte differentiation 4 1.5. TET protein family and TET1 6 1.6. 5-hydroxymethylation of deoxycytidine in cancer 7 1.7. Aim of this study 8 2. Materials and Methods 9 2.1. Cell culture and adipocyte differentiation 9 2.2. Vitamin C treatment 9 2.3. Oil-Red O staining 10 2.4. RNA isolation 10 2.5. Real-time RT-PCR 10 2.6. Genomic DNA isolation and dot-blot assay 11 2.7. Immunohistochemistry 12 2.8. Cell cycle analysis 12 2.9. Gene silencing using small interfering 13 2.10. Body composition analysis 13 2.11. NP-CGG immunization 13 3. Results 17 3.1. Expression of 5-hmC of sarcoma 17 3.2. Oil Red staining confirmed the differentiation of 3T3-L1 cells into adipocytes 17 3.3. Induction of Tet1-3 expression in the process of adipocytic differentiation of 3T3-L1 cells 18 3.4. Increased global 5-hydroxymethlation during adipogenic differentiation of 3T3-L1 cells 18 3.5. Changes in relative expression of Cebpα and Pparγ and Ebf-1 genes during adipogenic differentiation of 3T3L1 cells 18 3.6. Cell cycle analysis of the differentiation process 19 3.7. Regulation of adipocytic differentiation by Tet agonist vitamin C 19 3.8. Identification of the genes regulated by vitamin C during adipogenesis 20 3.9. Impact of Tet protein knockdown on adipogenesis 20 3.10. Validation of Tet1 target genes in Tets knockout model by RT-qPCR analysis 21 3.11. Body composition of WT and Tet1-/- mice 21 Supplementary Results 22 3.12. Knockout of Tet1 enhances germinal center (GC) formation 22 4. Discussion 23 4.1. Sarcoma formation is regulated by epigenetic mechanisms 23 4.2. Tet1 is involved cell differentiation 24 4.3. Tet1 regulates adipocytic differentiation via Cebpa and cell cycle of the proteins 24 4.4. Body composition of male and female mice 25 4.5. Loss Tet1 expression are involved in GC response 26 4.6. Tet plays a master role and control adipocytic differentiation 26 5. Figures and Tables 28 6. Supplementary Figure 45 Supplementary Figure 1. Knockout of Tet1 enhances GC formation. 45 7. Reference 46 | - |
dc.language.iso | en | - |
dc.title | Tet1和5-hydroxymethylcytosine在肉瘤中扮演的角色及其功能 | zh_TW |
dc.title | The role of TET1 and 5-hydroxymethylcytosine in the formation and function of sarcoma | en |
dc.type | Thesis | - |
dc.date.schoolyear | 106-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 張以承;張修豪;楊卿堯 | zh_TW |
dc.contributor.oralexamcommittee | ;; | en |
dc.subject.keyword | 脂肪肉瘤,脂肪分化,TET1,5-hmC,CEBPα, | zh_TW |
dc.subject.keyword | liposarcoma,adipocyte differentiation,TET1,5-hmC,CEBPα, | en |
dc.relation.page | 51 | - |
dc.identifier.doi | 10.6342/NTU201801822 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2018-07-24 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 病理學研究所 | - |
顯示於系所單位: | 病理學科所 |
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