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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 高淑芬 | |
dc.contributor.author | Chieh Chou | en |
dc.contributor.author | 周潔 | zh_TW |
dc.date.accessioned | 2021-06-16T09:54:06Z | - |
dc.date.available | 2019-02-24 | |
dc.date.copyright | 2017-02-24 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-01-10 | |
dc.identifier.citation | 1. Association, A.P., Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 5th ed. 2013, Washington, DC.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60069 | - |
dc.description.abstract | 動作發展是探索世界及主動社交互動的第一步,而運動缺陷常見於泛自閉症類群 (Autism spectrum disorder, ASD)中,且和ASD之核心症狀像是在社交能力以及人際溝通上的障礙有關聯,故運動神經元缺陷可能和ASD之致病機制相關。此研究利用患有ASD和Phelan-McDermid syndrome (PMS) 所建立的誘導型多能性幹細胞 (human induced pluripotent stem cells, hiPSC)分化成人類運動神經元作為細胞模式,提供此疾病一新穎的觀點。
利用帶有SHANK3基因缺陷之PMS-iPSC,我們獲得高純度的PMS患者的運動神經元,並發現運動神經元之產率不會受到疾病影響,但PMS患者的運動神經元之粒線體有氧氣消耗速率降低的現象。此外,ASD患者特有的拷貝數變異 (copy number variation, CNV) 包含對於基因造成複寫 (duplication) 或缺失 (deletion),在ASD患者周邊血液所建立的細胞株 (lymphoblastoid cell lines, LCLs) 中發現到基因表現量的改變,其中,SND1、 ABAT、 SLC38A10以及 RAB39B 之表現量上升,而 HDAC4、GNB1L、RPL10之表現量下降。 總結本研究,ASD特有的CNV在ASD的病因中扮演重要的角色,且運動神經元中的粒線體缺失可能與PMS以及ASD患者之運動缺失之致病機制有關聯,提供ASD之基礎或臨床研究不同的觀點。 | zh_TW |
dc.description.abstract | Autism spectrum disorder (ASD) presents motor deficits, which are related to core symptoms, impairments in social interaction and communication, suggesting motor neuron deficits may contribute to the etiology of ASD. Here, we proposed a novel point of view on ASD by using PMS-iPSC-derived motor neurons as an in vitro model.
Using PMS-iPSC harboring SHANK3 deletion, we obtained high-purity PMS-MNs and found that the PMS-MN generation was not altered. However, PMS-MNs had reduced oxygen consumption rate (OCR). In addition, we identified ASD-specific copy number variations (CNVs) and found CNVs, including duplication and deletion, of genes, influenced the expression level of genes in ASD-derived lymphoblastoid cell lines (LCLs) such as increased expression of SND1, ABAT, SLC38A1 and RAB39B and decreased expression of HDAC4, GNB1L, and RPL10. Combining results presented in this thesis, our data suggest that case-specific CNVs may play an essential role in the pathogenesis of ASD. Mitochondrial dysfunction may be a potential mechanistic link between motor deficits and contribute to core symptoms of PMS and ASD, which provided further insights into basic and clinical researches of ASD. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T09:54:06Z (GMT). No. of bitstreams: 1 ntu-106-R03454007-1.pdf: 3029851 bytes, checksum: a809f6fc95fa2090a090d3fa99862abd (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii ABSTRACT iii CONTENTS iv LIST OF FIGURES vi LIST OF TABLES vii ABBREVIATIONS viii Chapter 1 Introduction 1 Chapter 2 Materials and Methods 8 2.1 Case-specific CNVs 8 2.1.1 Identification 8 2.1.2 Validation 8 2.2 Human peripheral blood collection 9 2.3 Lymphoblastoid Cell lines, LCLs 9 2.4 Human iPSCs derivation and characterization 10 2.4.1 Isolation and maintenance of peripheral blood mononuclear cells (PBMCs) 10 2.4.2 Reprogramming PBMCs to iPSCs 10 2.4.3 iPSCs maintenance 11 2.4.4 Characterization of iPSCs 11 2.5 Motor neuron differentiation and maintenance 11 2.6 Teratoma formation 12 2.7 Immunocytochemistry (ICC), histochemistry and microscopy 13 2.8 Reverse transcription-polymerase chain reaction (RT-PCR) 14 2.9 TUNEL staining 14 2.10 XF24 assay 15 2.11 Statistical analysis 15 Chapter 3 Results 16 3.1 Case-specific CNVs in Taiwan ASD cohort 16 3.1.1 Identification and Validation of case-specific CNVs on 32 genes associated with neuropsychiatric disorders 16 3.1.2 mRNA expression of 13 genes in LCLs 17 3.2 PMS-iPSCs generation and characterization 17 3.3 Teratoma formation 18 3.4 PMS-MN differentiation 18 3.5 Mitochondrial function 19 3.6 Apoptosis 20 Chapter 4 Discussion 21 4.1 Identification of ASD candidate genes by case-specific CNV approach 21 4.2 5 ASD candidate genes 22 4.3 PMS-iPSC-derived motor neurons 25 4.4 Future work 26 REFERENCE 60 | |
dc.language.iso | en | |
dc.title | 探討自閉症類群之運動神經元缺失 | zh_TW |
dc.title | Modeling Motor Neuron Deficits in Autism Spectrum Disorder | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-1 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 郭紘志 | |
dc.contributor.oralexamcommittee | 莊樹諄,黃憲松 | |
dc.subject.keyword | 泛自閉症類群,Phelan-McDermid syndrome,誘導型多能性幹細胞,拷貝數變異,運動神經元,粒線體缺失,SHANK3基因, | zh_TW |
dc.subject.keyword | autism spectrum disorder,Phelan-McDermid syndrome,copy number variations,human induced pluripotent stem cells,motor neurons,mitochondrial dysfunction,SHANK3, | en |
dc.relation.page | 64 | |
dc.identifier.doi | 10.6342/NTU201700032 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-01-10 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 腦與心智科學研究所 | zh_TW |
顯示於系所單位: | 腦與心智科學研究所 |
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