請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63161完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 錢宗良 | |
| dc.contributor.author | Wei-Che Lin | en |
| dc.contributor.author | 林煒哲 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:25:44Z | - |
| dc.date.available | 2016-03-04 | |
| dc.date.copyright | 2013-03-04 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2013-01-21 | |
| dc.identifier.citation | Apfel C, Bauer F, Crettaz M, Forni L, Kamber M, Kaufmann F, LeMotte P, Pirson W, Klaus M. (1992). A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects. Proc Natl Acad Sci U S A 89, 7129-7133.
Artinger M, Blitz I, Inoue K, Tran U, Cho KW. (1997). Interaction of goosecoid and brachyury in Xenopus mesoderm patterning. Mech Dev 65, 187-196. Blum M, Gaunt SJ, Cho KW, Steinbeisser H, Blumberg B, Bittner D, De Robertis EM. (1992). Gastrulation in the mouse: the role of the homeobox gene goosecoid. Cell 69, 1097-1106. Bain G, Kitchens D, Yao M, Huettner JE, Gottlieb DI. (1995). Embryonic stem cells express neuronal properties in vitro. Dev Biol 168, 342-357. Bylund M, Andersson E, Novitch BG, Muhr J. (2003). Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat Neurosci 6, 1162-1168. Bain G, Ray WJ, Yao M, Gottlieb DI. (1996). Retinoic acid promotes neural and represses mesodermal gene expression in mouse embryonic stem cells in culture. Biochem Biophys Res Commun 223, 691-694. Barnea E, Bergman Y. (2000). Synergy of SF1 and RAR in activation of Oct-3/4 promoter. J Biol Chem 275, 6608-6619. Briscoe J, Ericson J. (2001). Specification of neuronal fates in the ventral neural tube. Curr Opin Neurobiol 11, 43-49. Chiu CP, Blau HM. (1985). 5-Azacytidine permits gene activation in a previously noninducible cell type. Cell 40, 417-424. Corcoran J, Maden M. (1999). Nerve growth factor acts via retinoic acid synthesis to stimulate neurite outgrowth. Nat Neurosci 2, 307-308. Corcoran J, Shroot B, Pizzey J, Maden M. (2000). The role of retinoic acid receptors in neurite outgrowth from different populations of embryonic mouse dorsal root ganglia. J Cell Sci 113, 2567-2574. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. (2001). Nuclear receptors and lipid physiology: opening the X-files. Science 294, 1866-1870. Corcoran J, So PL, Maden M. (2002). Absence of retinoids can induce motoneuron disease in the adult rat and a retinoid defect is present in motoneuron disease patients. J Cell Sci 115, 4735-4741. Chandran S, Kato H, Gerreli D, Compston A, Svendsen CN, Allen ND. (2003). FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathway. Development 130, 6599-6609. Chin MH, Mason MJ, Xie W, Volinia S, Singer M, Peterson C, Ambartsumyan G, Aimiuwu O, Richter L, Zhang J, et al. (2009). Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5, 111-123. Dani C, Smith AG, Dessolin S, Leroy P, Staccini L, Villageois P, Darimont C, Ailhaud G. (1997). Differentiation of embryonic stem cells into adipocytes in vitro. J Cell Sci 110, 1279-1285. Diez del Corral R, Storey KG. (2004). Opposing FGF and retinoid pathways: a signalling switch that controls differentiation and patterning onset in the extending vertebrate body axis. Bioessays 26, 857-869. Durston AJ, van der Wees J, Pijnappel WW, Godsave SF. (1998). Retinoids and related signals in early development of the vertebrate central nervous system. Curr Top Dev 40, 111-175. Dong D, Ruuska SE, Levinthal DJ, Noy N. (1999). Distinct roles for cellular retinoic acid-binding proteins I and II in regulating signaling by retinoic acid. J Biol Chem 274, 23695-23698. Evans MJ, Kaufman MH. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156. Eden S, Hashimshony T, Keshet I, Cedar H, Thorne AW. (1998). DNA methylation models histone acetylation. Nature 394, 842. Fraichard A, Chassande O, Bilbaut G, Dehay C, Savatier P, Samarut J. (1995). In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J Cell Sci 108, 3181-3188. Goncalves MB, Boyle J, Webber DJ, Hall S, Minger SL, Corcoran JP. (2005). Timing of the retinoid-signalling pathway determines the expression of neuronal markers in neural progenitor cells. Dev Biol 278, 60-70. Götz M, Barde YA. (2005). Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons. Neuron 46, 369 -372. Goncalves MB, Agudo M, Connor S, McMahon S, Minger SL, Maden M, Corcoran JP. (2009). Sequential RARbeta and alpha signalling in vivo can induce adult forebrain neural progenitor cells to differentiate into neurons through Shh and FGF signalling pathways. Dev Biol 326, 305-313. Herrmann BG, Labeit S, Poustka A, King TR, Lehrach H. (1990). Cloning of the T gene required in mesoderm formation in the mouse. Nature 343, 617-622. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318, 1920-1923. Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. (2008). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26, 795-797. Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R. (2009). Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595-601. Hu BY, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, Zhang SC. (2010). Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci U S A 107, 4335-4340. Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N. (2000). Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 6, 88-95. Jones-Villeneuve EM, Rudnicki MA, Harris JF, McBurney MW. (1983). Retinoic acid-induced neural differentiation of embryonal carcinoma cells. Mol Cell Biol 3, 2271-2279. Jiang YQ, Oblinger MM. (1992). Differential regulation of beta III and other tubulin genes during peripheral and central neuron development. J Cell Sci 103, 643-651. Kikuchi K, Tagami K, Hibi S, Yoshimura H, Tokuhara N, Tai K, Hida T, Yamauchi T, Nagai M. (2001). Syntheses and evaluation of quinoline derivatives as novel retinoic acid receptor alpha antagonists. Bioorg Med Chem Lett 11, 1215-1218. Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K. (2009). Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458, 771-775. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. (2009). Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4, 472-476. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, et al. (2010). Epigenetic memory in induced pluripotent stem cells. Nature 467, 285-290. Li W, Wei W, Zhu S, Zhu J, Shi Y, Lin T, Hao E, Hayek A, Deng H, Ding S. (2009). Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4, 16-19. Martin GR. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78, 7634-7638. Muhr J, Graziano E, Wilson S, Jessell TM, Edlund T. (1999). Convergent inductive signals specify midbrain, hindbrain, and spinal cord identity in gastrula stage chick embryos. Neuron 23, 689-702. Maden M. (2007). Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8, 755-765. Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, Bernstein BE, Jaenisch R, Lander ES, Meissner A. (2008). Dissecting direct reprogramming through integrative genomic analysis. Nature 454, 49-55. Ming GL, Song H. (2005). Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 28, 223-250. Muñoz-Sanjuán I, Brivanlou AH. (2002). NEURAL INDUCTION, THE DEFAULT MODEL AND EMBRYONIC STEM CELLS. Nat Rev Neurosci 3, 271-280. Mahony S, Mazzoni EO, McCuine S, Young RA, Wichterle H, Gifford DK. (2011). Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis. Genome Biol 12, R2. Mukherjee S, Thrasher AJ. (2011). iPSCs: Unstable origins? Mol Ther 19, 1188-1190. Novitch BG, Wichterle H, Jessell TM, Sockanathan S. (2003). A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuronspecification. Neuron 25, 81-95. Okazawa H, Okamoto K, Ishino F, Ishino-Kaneko T, Takeda S, Toyoda Y, Muramatsu M, Hamada H. (1991). The oct3 gene, a gene for an embryonic transcription factor, is controlled by a retinoic acid repressible enhancer. EMBO J 10, 2997-3005. Okita K, Ichisaka T, Yamanaka S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949-953. Pikarsky E, Sharir H, Ben-Shushan E, Bergman Y. (1994). Retinoic acid represses Oct-3/4 gene expression through several retinoic acid-responsive elements located in the promoter-enhancer region. Mol Cell Biol 14, 1026-1038. Russ AP, Wattler S, Colledge WH, Aparicio SA, Carlton MB, Pearce JJ, Barton SC, Surani MA, Ryan K, Nehls MC, et al. (2000). Eomesodermin is required for mouse trophoblast development and mesoderm formation. Nature 404, 95-99. Rhinn M, Dollé P. (2012). Retinoic acid signalling during development. Development 139, 843-858. Strübing C, Ahnert-Hilger G, Shan J, Wiedenmann B, Hescheler J, Wobus AM. (1995). Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons. Mech Dev 53, 275-287. Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. (2008). Induced pluripotent stem cells generated without viral integration. Science 322, 945-949. Spemann H, Mangold H. (1924). Uber die Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren . W Rou x ’ Arch f Entw d Organis u mikrosk Anat 100, 599-638. Shi Y, Desponts C, Do JT, Hahm HS, Schöler HR, Ding S. (2008). Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3, 568-574. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, et al. (2009). Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136, 964-977. Takahashi K, Yamanaka S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872. Wilkinson DG, Bhatt S, Herrmann BG. (1990). Expression pattern of the mouse T gene and its role in mesoderm formation. Nature 343, 657-659. Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, Cowling R, Wang W, Liu P, Gertsenstein M, et al. (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458, 766-770. Wilson SI, Edlund T. (2001). Neural induction: toward a unifying mechanism. Nat Neurosci 4, 1161-1168. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917-1920. Yusa K, Rad R, Takeda J, Bradley A. (2009). Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nat Methods 6, 363-369. Yu S, Levi L, Siegel R, Noy N. (2012). Retinoic Acid Induces Neurogenesis by Activating Both Retinoic Acid Receptors (RARs) and Peroxisome Proliferator -activated Receptor β/δ (PPARβ/δ). J Biol Chem 287, 42195-42205. Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, et al. (2009). Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4, 381-384. Zhao T, Zhang ZN, Rong Z, Xu Y. (2011). Immunogenicity of induced pluripotent stem cells. Nature 474, 212-215. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63161 | - |
| dc.description.abstract | 胚胎幹細胞是一種從囊胚時期內細胞團所分離出來的多能性幹細胞，擁有自我複製及分化成三胚層所有細胞種類的能力。而誘導式多能幹細胞是利用四個轉錄因子Oct4、Sox2、Klf4、c-Myc轉染到體細胞中，利用後續的再程序化作用使體細胞回到原先類似胚胎幹細胞的狀態。由於誘導式多能幹細胞是從體細胞轉變而來的，取得比較便利同時也免除了倫理道德上的爭議，因此在發育學研究、藥物研發與篩選以及運用在自體細胞移植上，要比胚胎幹細胞更具有優勢。
在本研究中，我們探討小鼠胚胎幹細胞與誘導式多能幹細胞在神經分化上的差異性。在體外分化試驗中，我們利用了神經分化的誘導物“維他命A酸”來誘導兩株幹細胞分化成神經細胞。在經過維他命A酸處理過後，我們發現小鼠胚胎幹細胞比誘導式多能幹細胞分化出更多具有類似神經突出的細胞。為了釐清這種現象，我們利用即時定量聚合酶連鎖反應以及免疫細胞化學染色法分析兩種幹細胞所分化出來的細胞。分析結果顯示在維他命A酸處理過後，誘導式多能幹細胞比胚胎幹細胞分化出更多的中胚層的細胞。初步顯示誘導式多能幹細胞比胚胎幹細胞更容易往中胚層分化。另一方面我們也探討了維他命A酸受體在兩株幹細胞間的表現量，透過西方墨點法的分析，我們發現維他命A酸α型受體以及維他命A酸β型受體在兩株幹細胞間的表現量有很大的差異。在利用維他命A酸誘導分化之前與之後，維他命A酸α型受體在胚胎幹細胞的表現量皆高於誘導式多能幹細胞。而維他命A酸β型受體的表現量則是誘導式多能幹細胞高於胚胎幹細胞，然而在維他命A酸處理過後，維他命A酸β型受體在誘導式多能幹細胞中的表現量明顯地下降許多，並在誘導分化後第四天跟胚胎幹細胞相比達到顯著差異。為了更深入探討維他命A酸受體在神經分化上的作用，我們利用維他命A酸α型受體的抑制劑來抑制維他命A酸α型受體的活性。經過維他命A酸α型受體抑制劑的處理之後，我們發現在兩株幹細胞中維他命A酸α型受體及神經細胞特有的骨架蛋白 “β-微管蛋白III” 的基因表現量皆有下降的趨勢。並且在誘導分化後第四天和單獨處理維他命A酸的實驗組別相比，達到統計上的顯著差異。 總結研究結果，我們認為誘導式多能幹細胞具有較易往中胚層分化的特性，而維他命A酸α及β型受體在兩株幹細胞內表現量的差異，直接或是間接地影響這兩株幹細胞的神經分化。 | zh_TW |
| dc.description.abstract | Pluripotent stem cells possess the powerful ability to replicate indefinitely and can differentiate into various cell types derived from three germ layers. It has been reported that induced pluripotent stem cells (iPSCs) reprogrammed from somatic fibroblasts have been generated by transfecting four transcription factors including Oct4, Sox2, Klf4 and c-Myc. After the reprogram, iPSCs has provided great advantages in many applications, such as developmental studies, drug screening, and autologous cell transplantation.
In this study, we compared the neural differentiation ability between two pluripotent stem cells, mouse embryonic stem cells (mESCs) and mouse induced pluripotent stem cells (miPSCs) with the neural inducer “retinoic acid (RA)” treatment. After RA-induction, both mESC- and miPSC-derived cells exhibited neuron-like processes. The potency of neurodifferentiation was different between the mESCs and the miPSCs after RA-induction. In order to clarify this phenomenon, we further characterized the mESC- and miPSC-derived cells by reverse transcription polymerase chain reaction (RT-PCR)/quantitative polymerase chain reaction (qPCR) and immunocytochemical approaches. More mesodermal lineage cells could be found from the miPSCs after RA-induction. Protein levels of retinoic acid receptors (RARs) involved in RA signaling pathway were also examined in both stem cells. The protein level of RARα in the mESCs was higher than that in the miPSCs. Using the RARα antagonist to attenuate RARα activity resulted in down-regulation of RARα and β-tubulin III in both stem cells. On the other hand, the level of RARβ was higher in the miPSCs before RA treatment, but was dramatically down-regulated after RA-induction in comparison with the mESCs. Our data indicated that the propensity of neuroectodermal differentiation could be correlated with the different distributions of RARα and RARβ induced by RA treatment between the mESCs and the miPSCs we used. We suggested that the cell memory of the miPSCs could be one of the key factors triggered the mesodermal differentiation. The neuroectodermal differentiation could be easily induced by RA treatment via RAR signal pathway in the pluripotent mESCs. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:25:44Z (GMT). No. of bitstreams: 1 ntu-101-R99446014-1.pdf: 6484841 bytes, checksum: 5a29d074586ead83f7d93a1247102345 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 口試委員會審定書
誌謝 摘要Abstract Table of Contents Table of Figures Introduction Materials and methods Results Discussion Table 1 References Appendix | |
| dc.language.iso | en | |
| dc.subject | 小鼠胚胎幹細胞 | zh_TW |
| dc.subject | 誘導式多能幹細胞 | zh_TW |
| dc.subject | 神經分化 | zh_TW |
| dc.subject | mouse induced pluripotent stem cells | en |
| dc.subject | mouse embryonic stem cells | en |
| dc.subject | neural differentiation | en |
| dc.title | 探討小鼠胚胎幹細胞與誘導式多能幹細胞之分化差異 | zh_TW |
| dc.title | Study of Differences in Differentiation between Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 郭紘志,陳玉玲 | |
| dc.subject.keyword | 小鼠胚胎幹細胞,誘導式多能幹細胞,神經分化, | zh_TW |
| dc.subject.keyword | mouse embryonic stem cells,mouse induced pluripotent stem cells,neural differentiation, | en |
| dc.relation.page | 50 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-01-22 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨生物細胞學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-101-1.pdf 未授權公開取用 | 6.33 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。