請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73783完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 康照洲(Jaw-Jou Kang) | |
| dc.contributor.author | Meng-Wei Lin | en |
| dc.contributor.author | 林孟緯 | zh_TW |
| dc.date.accessioned | 2021-06-17T08:10:09Z | - |
| dc.date.available | 2021-02-23 | |
| dc.date.copyright | 2021-02-23 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-01-29 | |
| dc.identifier.citation | Abbott, B. D., et al. (1995). 'Developmental expression of two members of a new class of transcription factors: I. Expression of aryl hydrocarbon receptor in the C57BL/6N mouse embryo.' Dev Dyn 204(2): 133-143. Adachi, J., et al. (2001). 'Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine.' J Biol Chem 276(34): 31475-31478. Akaogi, K., et al. (2009). 'KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERalpha.' Oncogene 28(32): 2894-2902. Alexander, D. L., et al. (1998). 'Aryl-hydrocarbon receptor is an inhibitory regulator of lipid synthesis and of commitment to adipogenesis.' J Cell Sci 111 ( Pt 22): 3311-3322. Angelos, M. G., et al. (2017). 'Aryl hydrocarbon receptor inhibition promotes hematolymphoid development from human pluripotent stem cells.' Blood 129(26): 3428-3439. Anokye-Danso, F., et al. (2011). 'Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.' Cell Stem Cell 8(4): 376-388. Avilion, A. A., et al. (2003). 'Multipotent cell lineages in early mouse development depend on SOX2 function.' Genes Dev 17(1): 126-140. Barroso-delJesus, A., et al. (2011). 'The Nodal inhibitor Lefty is negatively modulated by the microRNA miR-302 in human embryonic stem cells.' Faseb j 25(5): 1497-1508. Blankenship, A. L., et al. (1993). '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accelerates differentiation of murine preimplantation embryos in vitro.' Reproductive Toxicology 7(3): 255-261. Boroviak, T. and J. Nichols (2014). 'The birth of embryonic pluripotency.' Philos Trans R Soc Lond B Biol Sci 369(1657). Bouvier, J. D. and T. N. Seyfried (1989). 'Ganglioside composition of normal and mutant mouse embryos.' J Neurochem 52(2): 460-466. Boyer, L. A., et al. (2005). 'Core transcriptional regulatory circuitry in human embryonic stem cells.' Cell 122(6): 947-956. Brambrink, T., et al. (2008). 'Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells.' Cell Stem Cell 2(2): 151-159.Adachi, J., et al. (2001). 'Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine.' J Biol Chem 276(34): 31475-31478. Briggs, R. and T. J. King (1952). 'Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs.' Proc Natl Acad Sci U S A 38(5): 455-463. Briggs, R. and T. J. King (1957). 'Changes in the nuclei of differentiating endoderm cells as revealed by nuclear transplantation.' Journal of Morphology 100(2): 269-311. Brown, K. A., et al. (2008). 'Identification of novel Smad2 and Smad3 associated proteins in response to TGF-beta1.' J Cell Biochem 105(2): 596-611. Cantone, I. and A. G. Fisher (2013). 'Epigenetic programming and reprogramming during development.' Nat Struct Mol Biol 20(3): 282-289. Carvajal-Gonzalez, J. M., et al. (2009). 'The Dioxin Receptor Regulates the Constitutive Expression of the Vav3 Proto-Oncogene and Modulates Cell Shape and Adhesion.' Molecular Biology of the Cell 20(6): 1715-1727. Charron, J., et al. (1992). 'Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene.' Genes Dev 6(12a): 2248-2257. Chen, X., et al. (2001). 'Kruppel-like factor 4 (gut-enriched Kruppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle.' J Biol Chem 276(32): 30423-30428. Chen, X., et al. (2003). 'Transcriptional profiling of Kruppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.' J Mol Biol 326(3): 665-677. Chen, Y. J., et al. (2008). 'Nuclear Krüppel-like factor 4 expression is associated with human skin squamous cell carcinoma progression and metastasis.' Cancer Biol Ther 7(5): 777-782. Cheng, X., et al. (2020). 'NHC-gold compounds mediate immune suppression through induction of AHR-TGFβ1 signalling in vitro and in scurfy mice.' Communications Biology 3(1): 10. Chester, M. A. (1998). 'IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycolipids--recommendations 1997.' Eur J Biochem 257(2): 293-298. Christophersen, N. S. and K. Helin (2010). 'Epigenetic control of embryonic stem cell fate.' J Exp Med 207(11): 2287-2295. Collignon J, K. P., et al. (1990). 'A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes.' Nature 346: 245-250. Cox, P. G., et al. (2004). 'Radiofrequency ablation of airway smooth muscle for sustained treatment of asthma: preliminary investigations.' Eur Respir J 24(4): 659-663. Davis, A. C., et al. (1993). 'A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice.' Genes Dev 7(4): 671-682. Davis, R. L., et al. (1987). 'Expression of a single transfected cDNA converts fibroblasts to myoblasts.' Cell 51(6): 987-1000. Dey, A. and D. W. Nebert (1998). 'Markedly increased constitutive CYP1A1 mRNA levels in the fertilized ovum of the mouse.' Biochem Biophys Res Commun 251(2): 657-661. Elizondo, G., et al. (2000). 'Altered cell cycle control at the G(2)/M phases in aryl hydrocarbon receptor-null embryo fibroblast.' Mol Pharmacol 57(5): 1056-1063. Emmons, R. B., et al. (1999). 'The spineless-aristapedia and tango bHLH-PAS proteins interact to control antennal and tarsal development in Drosophila.' Development 126(17): 3937-3945. Evans, M. (1981). 'Origin of mouse embryonal carcinoma cells and the possibility of their direct isolation into tissue culture.' Reproduction 62(2): 625. Evans, M. J. and M. H. Kaufman (1981). 'Establishment in culture of pluripotential cells from mouse embryos.' Nature 292(5819): 154-156. Fernandez-Salguero, P., et al. (1995). 'Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor.' Science 268(5211): 722-726. Fernandez-Salguero, P. M., et al. (1997). 'Lesions of aryl-hydrocarbon receptor-deficient mice.' Vet Pathol 34(6): 605-614. Folmes, C. D., et al. (2011). 'Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming.' Cell Metab 14(2): 264-271. Fong, C. Y., et al. (2009). 'Separation of SSEA-4 and TRA-1-60 labelled undifferentiated human embryonic stem cells from a heterogeneous cell population using magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS).' Stem Cell Rev Rep 5(1): 72-80. Fong H, et al. (2008). 'Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells.' Stem Cells 26: 1931-1938. Foster, K. A., et al. (1998). 'Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism.' Exp Cell Res 243(2): 359-366. Fukunaga, M., et al. (1995). 'Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov., isolated from the ixodid tick Ixodes persulcatus, the vector for Lyme disease in Japan.' Int J Syst Bacteriol 45(4): 804-810. Gaido, K. W., et al. (1992). '2,3,7,8-Tetrachlorodibenzo-p-dioxin-dependent regulation of transforming growth factors-alpha and -beta 2 expression in a human keratinocyte cell line involves both transcriptional and post-transcriptional control.' J Biol Chem 267(34): 24591-24595. Gasiewicz, T. A., et al. (2008). 'Expression and activity of aryl hydrocarbon receptors in development and cancer.' Crit Rev Eukaryot Gene Expr 18(4): 279-321. Ghaleb, A. M., et al. (2007). 'Haploinsufficiency of Krüppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis.' Cancer Res 67(15): 7147-7154. Gonzalez, F. J. and P. Fernandez-Salguero (1998). 'The aryl hydrocarbon receptor: studies using the AHR-null mice.' Drug Metab Dispos 26(12): 1194-1198. Goolam, M., et al. (2016). 'Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos.' Cell 165(1): 61-74. Gubbay, J., et al. (1990). 'A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes.' Nature 346(6281): 245-250. Gurdon, J. B. (1962). 'The Developmental Capacity of Nuclei taken from Intestinal Epithelium Cells of Feeding Tadpoles.' Journal of Embryology and Experimental Morphology 10(4): 622-640. H. Xie, et al. (2004). 'Stepwise reprogramming of B cells into macrophages.' Cell 117: pp. 663-676. Hahn, M. E. (2002). 'Aryl hydrocarbon receptors: diversity and evolution.' Chem Biol Interact 141(1-2): 131-160. Hakomori, S. I. (2010). 'Glycosynaptic microdomains controlling tumor cell phenotype through alteration of cell growth, adhesion, and motility.' FEBS Lett 584(9): 1901-1906. Hatton, K. S., et al. (1996). 'Expression and activity of L-Myc in normal mouse development.' Mol Cell Biol 16(4): 1794-1804. Hayashi, S., et al. (1995). 'Synthetic hexa- and heptapeptides that inhibit IL-8 from binding to and activating human blood neutrophils.' The Journal of Immunology 154(2): 814-824. Hu, S., et al. (2013). 'MicroRNA-302 increases reprogramming efficiency via repression of NR2F2.' Stem Cells 31(2): 259-268. Hu, W., et al. (2013). 'Activation of aryl hydrocarbon receptor (ahr) by tranilast, an anti-allergy drug, promotes miR-302 expression and cell reprogramming.' J Biol Chem 288(32): 22972-22984. Jain, S., et al. (1998). 'Expression of ARNT, ARNT2, HIF1 alpha, HIF2 alpha and Ah receptor mRNAs in the developing mouse.' Mech Dev 73(1): 117-123. Jiang, J., et al. (2008). 'A core Klf circuitry regulates self-renewal of embryonic stem cells.' Nat Cell Biol 10(3): 353-360. Kallapur, S., et al. (1999). 'Strain dependency of TGFbeta1 function during embryogenesis.' Mol Reprod Dev 52(4): 341-349. Karpowicz, P., et al. (2009). 'E-Cadherin Regulates Neural Stem Cell Self-Renewal.' The Journal of Neuroscience 29(12): 3885-3896. Kim, H. H., et al. (2009). 'HuR recruits let-7/RISC to repress c-Myc expression.' Genes Dev 23(15): 1743-1748. Kim, M. D., et al. (2006). 'The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons.' Genes Dev 20(20): 2806-2819. Knoepfler, P. S., et al. (2002). 'N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation.' Genes Dev 16(20): 2699-2712. Ko, C. I., et al. (2014). 'Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells.' Stem Cell Res 12(1): 296-308. Koche, R. P., et al. (2011). 'Reprogramming factor expression initiates widespread targeted chromatin remodeling.' Cell Stem Cell 8(1): 96-105. Ky, N., et al. (2009). 'KLF4 suppresses HDACi induced caspase activation and the SAPK pathway by targeting p57Kip2.' Apoptosis 14(9): 1095-1107. Lahvis, G. P., et al. (2000). 'Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice.' Proceedings of the National Academy of Sciences 97(19): 10442-10447. Lahvis, G. P., et al. (2005). 'The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse.' Mol Pharmacol 67(3): 714-720. Laiosa, C. V., et al. (2006). 'Determinants of lymphoid-myeloid lineage diversification.' Annu Rev Immunol 24: 705-738. Laiosa, M. D., et al. (2016). 'Effects of Developmental Activation of the Aryl Hydrocarbon Receptor by 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Long-term Self-renewal of Murine Hematopoietic Stem Cells.' Environ Health Perspect 124(7): 957-965. Law, M. H., et al. (2015). 'Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.' Nat Genet 47(9): 987-995. Lee, S. H., et al. (2010). 'Dynamic methylation and expression of Oct4 in early neural stem cells.' J Anat 217(3): 203-213. Lehmann, G. M., et al. (2011). 'The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation.' The American Journal of Pathology 178(4): 1556-1567. Lengner, C. J., et al. (2007). 'Oct4 expression is not required for mouse somatic stem cell self-renewal.' Cell Stem Cell 1(4): 403-415. Li, Z., et al. (2010). 'KLF4 promotes hydrogen-peroxide-induced apoptosis of chronic myeloid leukemia cells involving the bcl-2/bax pathway.' Cell Stress Chaperones 15(6): 905-912. Liao, B., et al. (2011). 'MicroRNA cluster 302-367 enhances somatic cell reprogramming by accelerating a mesenchymal-to-epithelial transition.' J Biol Chem 286(19): 17359-17364. Lindsey, P. A., et al. (2012). 'The Significance of African Lions for the Financial Viability of Trophy Hunting and the Maintenance of Wild Land.' PLOS ONE 7(1): e29332. Lingwood, C. A. (2011). 'Glycosphingolipid functions.' Cold Spring Harb Perspect Biol 3(7). Lund, A. K., et al. (2003). 'Cardiac hypertrophy in Aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin-1, and mean arterial blood pressure.' Toxicology and Applied Pharmacology 193(2): 177-187. Mani, S. A., et al. (2008). 'The epithelial-mesenchymal transition generates cells with properties of stem cells.' Cell 133(4): 704-715. Massagué, J. and D. Wotton (2000). 'Transcriptional control by the TGF-beta/Smad signaling system.' Embo j 19(8): 1745-1754. Masuda, Y. (1985). 'Health status of Japanese and Taiwanese after exposure to contaminated rice oil.' Environ Health Perspect 60: 321-325. Masui S, et al. (2007). 'Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells.' Nat Cell Biol 9: 625-635. Mengoni, M., et al. (2020). 'The aryl hydrocarbon receptor promotes inflammation-induced dedifferentiation and systemic metastatic spread of melanoma cells.' International Journal of Cancer 147(10): 2902-2913. Meyer, B. K. and G. H. Perdew (1999). 'Characterization of the AhR-hsp90-XAP2 core complex and the role of the immunophilin-related protein XAP2 in AhR stabilization.' Biochemistry 38(28): 8907-8917. Meyer, N. and L. Z. Penn (2008). 'Reflecting on 25 years with MYC.' Nat Rev Cancer 8(12): 976-990. Miyoshi, N., et al. (2011). 'Reprogramming of mouse and human cells to pluripotency using mature microRNAs.' Cell Stem Cell 8(6): 633-638. Moens, C. B., et al. (1992). 'A targeted mutation reveals a role for N-myc in branching morphogenesis in the embryonic mouse lung.' Genes Dev 6(5): 691-704. Morales-Hernández, A., et al. (2016). 'Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor.' Nucleic Acids Research 44(10): 4665-4683. Nagy, A., et al. (1998). 'Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles.' Curr Biol 8(11): 661-664. Nakagawa, M., et al. (2008). 'Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts.' Nat Biotechnol 26(1): 101-106. Nakaya, Y. and G. Sheng (2008). 'Epithelial to mesenchymal transition during gastrulation: an embryological view.' Dev Growth Differ 50(9): 755-766. Nichols J, et al. (1998). 'Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.' Cell 95: 379-391. Nieto, M. A. (2011). 'The ins and outs of the epithelial to mesenchymal transition in health and disease.' Annu Rev Cell Dev Biol 27: 347-376. Niwa, H., et al. (2000). 'Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.' Nat Genet 24(4): 372-376. Okudaira, N., et al. (2013). 'Long interspersed element-1 is differentially regulated by food-borne carcinogens via the aryl hydrocarbon receptor.' Oncogene 32(41): 4903-4912.Elizondo, G., et al. (2000). 'Altered cell cycle control at the G(2)/M phases in aryl hydrocarbon receptor-null embryo fibroblast.' Mol Pharmacol 57(5): 1056-1063. Opitz, C. A., et al. (2011). 'An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor.' Nature 478(7368): 197-203. Peters, J. M. and L. M. Wiley (1995). 'Evidence that murine preimplantation embryos express aryl hydrocarbon receptor.' Toxicol Appl Pharmacol 134(2): 214-221. Poland, A., et al. (1976). 'Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase.' The Journal of biological chemistry 251 16: 4936-4946. Qin, H. and J. A. Powell-Coffman (2004). 'The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development.' Dev Biol 270(1): 64-75. Ramos, K. S., et al. (2011). 'Epigenetic control of embryonic renal cell differentiation by L1 retrotransposon.' Birth Defects Res A Clin Mol Teratol 91(8): 693-702. Rannug, A., et al. (1987). 'Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances.' J Biol Chem 262(32): 15422-15427. Reyes-Reyes, E. M., et al. (2016). 'The aryl hydrocarbon receptor agonist benzo(a)pyrene reactivates LINE-1 in HepG2 cells through canonical TGF-β1 signaling: implications in hepatocellular carcinogenesis.' Am J Cancer Res 6(5): 1066-1077. Rosner, B., et al. (1990). 'Correction of logistic regression relative risk estimates and confidence intervals for measurement error: the case of multiple covariates measured with error.' Am J Epidemiol 132(4): 734-745. Rowland, B. D., et al. (2005). 'The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene.' Nat Cell Biol 7(11): 1074-1082. Sakaki-Yumoto, M., et al. (2013). 'Smad2 is essential for maintenance of the human and mouse primed pluripotent stem cell state.' J Biol Chem 288(25): 18546-18560. Samavarchi-Tehrani, P., et al. (2010). 'Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming.' Cell Stem Cell 7(1): 64-77. Saric, N., et al. (2020). 'The AHR pathway represses TGFbeta-SMAD3 signalling and has a potent tumour suppressive role in SHH medulloblastoma.' Sci Rep 10(1): 148. Sartor, M. A., et al. (2009). 'Genomewide analysis of aryl hydrocarbon receptor binding targets reveals an extensive array of gene clusters that control morphogenetic and developmental programs.' Environ Health Perspect 117(7): 1139-1146. Shie, J. L., et al. (2000). 'Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.' Am J Physiol Gastrointest Liver Physiol 279(4): G806-814. Schepers GE, et al. (2002). 'Twenty pairs of sox:extent, homology, and nomenclature of the mouse and human sox transcription factor gene families.' Dev Cell 3: 167-170. Schöler, H. R., et al. (1990). 'Oct-4: a germline-specific transcription factor mapping to the mouse t-complex.' Embo j 9(7): 2185-2195. Shi, Y. and J. Massagué (2003). 'Mechanisms of TGF-beta signaling from cell membrane to the nucleus.' Cell 113(6): 685-700. Simonian, P. L., et al. (2010). 'γδ T cells protect against lung fibrosis via IL-22.' J Exp Med 207(10): 2239-2253. Sinal, C. J. and J. R. Bend (1997). 'Aryl hydrocarbon receptor-dependent induction of cyp1a1 by bilirubin in mouse hepatoma hepa 1c1c7 cells.' Mol Pharmacol 52(4): 590-599. Sinclair, A. H., et al. (1990). 'A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif.' Nature 346(6281): 240-244. Singh, N. P., et al. (2011). 'Activation of aryl hydrocarbon receptor (AhR) leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis.' PLOS ONE 6(8): e23522. Smith, A. G., et al. (1988). 'Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides.' Nature 336(6200): 688-690. Stadtfeld, M. and K. Hochedlinger (2010). 'Induced pluripotency: history, mechanisms, and applications.' Genes Dev 24(20): 2239-2263. Stanford, E. A., et al. (2016). 'Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis.' Mol Cancer Res 14(8): 696-706. Stanford, E. A., et al. (2016). 'The role of the aryl hydrocarbon receptor in the development of cells with the molecular and functional characteristics of cancer stem-like cells.' BMC Biology 14(1): 20. Stanton, B. R., et al. (1992). 'Loss of N-myc function results in embryonic lethality and failure of the epithelial component of the embryo to develop.' Genes Dev 6(12a): 2235-2247. Subramanyam, D., et al. (2011). 'Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells.' Nat Biotechnol 29(5): 443-448. Tada, M., et al. (2001). 'Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells.' Curr Biol 11(19): 1553-1558. Takahashi, K., et al. (2007). 'Induction of pluripotent stem cells from adult human fibroblasts by defined factors.' Cell 131(5): 861-872. Takahashi, K. and S. Yamanaka (2006). 'Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors.' Cell 126(4): 663-676. Talmasov, D., et al. (2015). 'Krüppel-like factor 4 is a radioprotective factor for the intestine following γ-radiation-induced gut injury in mice.' American Journal of Physiology-Gastrointestinal and Liver Physiology 308(2): G121-G138. Thiery, J. P., et al. (2009). 'Epithelial-mesenchymal transitions in development and disease.' Cell 139(5): 871-890. Tronnier, M., et al. (1995). 'Ultraviolet irradiation induces acute changes in melanocytic nevi.' J Invest Dermatol 104(4): 475-478. Thomson, J. A., et al. (1998). 'Embryonic stem cell lines derived from human blastocysts.' Science 282(5391): 1145-1147. Tronnier, M., et al. (1995). 'Ultraviolet irradiation induces acute changes in melanocytic nevi.' J Invest Dermatol 104(4): 475-478. Unnisa, Z., et al. (2016). 'Aryl Hydrocarbon Receptor Deficiency in an Exon 3 Deletion Mouse Model Promotes Hematopoietic Stem Cell Proliferation and Impacts Endosteal Niche Cells.' Stem Cells Int 2016: 4536187. Viswanathan, M., et al. (2008). 'Outcomes of maternal weight gain.' Evid Rep Technol Assess (Full Rep)(168): 1-223. Wakefield, L. M. and A. B. Roberts (2002). 'TGF-beta signaling: positive and negative effects on tumorigenesis.' Curr Opin Genet Dev 12(1): 22-29. Wang, Q., et al. (2013). 'Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis.' Environ Health Perspect 121(11-12): 1334-1343. Wang, Q., et al. (2016). 'Ah Receptor Activation by Dioxin Disrupts Activin, BMP, and WNT Signals During the Early Differentiation of Mouse Embryonic Stem Cells and Inhibits Cardiomyocyte Functions.' Toxicol Sci 149(2): 346-357. Wang, X. and J. Dai (2010). 'Concise review: isoforms of OCT4 contribute to the confusing diversity in stem cell biology.' Stem Cells 28(5): 885-893. Whiteman, D. C., et al. (2016). 'The Growing Burden of Invasive Melanoma: Projections of Incidence Rates and Numbers of New Cases in Six Susceptible Populations through 2031.' J Invest Dermatol 136(6): 1161-1171. Whitlock, N. C., et al. (2011). 'Resveratrol-induced apoptosis is mediated by early growth response-1, Krüppel-like factor 4, and activating transcription factor 3.' Cancer Prev Res (Phila) 4(1): 116-127. Wu, Q., et al. (2002). 'Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on preimplantation mouse embryos.' Toxicology 174(2): 119-129. Wilmut, I., et al. (1997). 'Viable offspring derived from fetal and adult mammalian cells.' Nature 385(6619): 810-813. Xu, J., et al. (2010). 'MYC and Breast Cancer.' Genes Cancer 1(6): 629-640. Xu-Monette, Z. Y., et al. (2016). 'Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma.' Blood 128(26): 3083-3100. Yan, J., et al. (2019). 'Aryl Hydrocarbon Receptor Signaling Prevents Activation of Hepatic Stellate Cells and Liver Fibrogenesis in Mice.' Gastroenterology 157(3): 793-806.e714. Ying, Q.-L., et al. (2008). 'The ground state of embryonic stem cell self-renewal.' Nature 453(7194): 519-523. Yoon, H. S., et al. (2003). 'Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage.' J Biol Chem 278(4): 2101-2105. Yoon, H. S., et al. (2005). 'Krüppel-like factor 4 prevents centrosome amplification following γ-irradiation-induced DNA damage.' Oncogene 24(25): 4017-4025. Yoon, H. S. and V. W. Yang (2004). 'Requirement of Krüppel-like Factor 4 in Preventing Entry into Mitosis following DNA Damage.' Journal of Biological Chemistry 279(6): 5035-5041. Yu, J., et al. (2007). 'Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells.' Science 318(5858): 1917-1920. Yu, R. K. (1994). 'Development regulation of ganglioside metabolism.' Prog Brain Res 101: 31-44. Zafarana, G., et al. (2009). 'Specific knockdown of OCT4 in human embryonic stem cells by inducible short hairpin RNA interference.' Stem Cells 27(4): 776-782. Zaher, H., et al. (1998). 'The involvement of aryl hydrocarbon receptor in the activation of transforming growth factor-beta and apoptosis.' Mol Pharmacol 54(2): 313-321. Zhang, L., et al. (2010). 'The impact of C-MYC gene expression on gastric cancer cell.' Mol Cell Biochem 344(1-2): 125-135. Zhang, W., et al. (2000). 'The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.' J Biol Chem 275(24): 18391-18398. Zhou, Q., et al. (2008). 'In vivo reprogramming of adult pancreatic exocrine cells to β-cells.' Nature 455(7213): 627-632Mol Cell Biochem 344(1-2): 125-135. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73783 | - |
| dc.description.abstract | 誘導多能性幹細胞 (iPSCs) 為細胞較原始的狀態，可以重啟細胞再編程 (cell reprogramming) 分化成不同胚層。先前研究發現將細胞過量表達轉錄因子OSKM (Oct3/4、Sox2、Klf4、c-MYC) 後，已分化細胞重啟多能性，使其成為具有幹細胞特性之iPSCs。多環芳香烴受體 (Aryl hydrocarbon receptor, AHR是受戴奧辛等配體調控的轉錄因子，在藥物代謝和致癌反應中，扮演關鍵的角色。內生性AHR調控許多生理功能，像是細胞增生、細胞型態、細胞附著以及細胞移行，近來則發現AHR具有負調控細胞多能性的新穎功能，但其機制尚未清楚。我們在A549肺癌細胞株中將AHR基因以CRISPR/Cas9技術進行基因編輯加以剔除後，發現細胞具有類似iPSC的特性：在評估多能性 (Pluripotency) 的代表試驗─類胚體 (embryoid bodies) 的產生中，發現AHR-KO後會產生直徑較大且形態完整的類胚體；進一步在免疫螢光染色實驗中發現，AHR-KO細胞中代表多能性標誌的醣蛋白SSEA4和TRA-1-60，不論是在細胞質和細胞核中都較野生型A549表現多，且在多能分化性基因Oct4、Sox2、Klf4、c-Myc和Nanog的表現都有顯著增加的情況。由於細胞處於幹細胞狀態時，分化能力會受到限制，接著以MTT試驗方法觀察細胞生長的現象：發現AHR-KO細胞增生速率下降。此外在調控細胞多能性和細胞生長的TGF/Smad路徑中發現：在AHR基因剔除後，促纖維化的Smad3及磷酸化表現抑制；抗纖維化的Smad2 及磷酸化表現活化，在給予TGF纖維化刺激因子的情況下，AHR-KO細胞的移行能力和膠原蛋白的轉錄活性皆較野生型A549大幅減弱，顯示具有抗纖維化的特性。我們的研究結果顯示：A549經過CRISPR/Cas9方法AHR基因剔除後，細胞會再編程，成為具誘導性多能幹細胞特性的細胞，且具有抗纖維化的特性。
| zh_TW |
| dc.description.abstract | Induced pluripotent stem cells (iPSCs) were initially generated by introducing reprogramming factors via integrating viral vectors. Nonetheless, there was a clinical concern about iPSCs on account of the potential for insertional mutangenesis caused by the integration on transgenes into the genome of host cells. To make iPSCs more clinically available, various non-inegrating reprogramming methods have been developed to circumvent the risk of insertional mutagenesis and genetic alterations. While sensing the outer cell environment, the aryl hydrocarbon receptor (AHR) involved in embryonic development has a fine-tuned pattern to regulate the stemness in cell. Here, we present that AHR-Knockout (AHR-KO) by CRISPR/Cas9 system triggers cell reprogramming into iPSCs. The use of integration-free methods could avoid genomic insertion, therefore reducing risk when human iPSCs are used for clinical applications. In the first place, we employed CRISPR/Cas9 system to establish the AHR-KO clone from A549. Intriguingly, we found that AHR-KO cells had the characteristic of IPSCs. With the classical cell pluripotency methods, embryoid bodies (EB) formation assay, It showed that AHR-KO cells formed more complicated EB. We also found that AHR-KO presented more pluripotency marker, SSEA-4 and TRA-1-60 in the cell membrane or cytosol. Moreover, pluripotency gene expression level increased in AHR-KO cells. Owing to stem cell specific characteristics imply low cell growth rate, we found the cell proliferation rate decreased in AHR-KO cells. Furthermore, we analyzed the cell behavior, migration ability decreased in AHR-KO cells. Smad2 protein expression urged in AHR-KO cell, and Smad2 phosphorylation protein expression also increased; however, Smad3 and Smad3 phosphorylation protein expression declined. In the previous studies showed that Smad3 was participated in lung fibrosis progression. In order to assess fibrosis amelioration capability, we used wt-A549 and A549-AHR KO cells treated with transforming growth factor- (TGF-) to induce fibrosis. We suggest that Smad 2 and Smad2 phosphorylation protein expression decreased in AHR-KO cells. We may develop reprogrammed cell by CRISPR/Cas9 against tissue fibrosis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T08:10:09Z (GMT). No. of bitstreams: 1 U0001-2901202111101400.pdf: 3028383 bytes, checksum: 8187a852001bfa8f47a9081b1a70b450 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 誌謝 II 中文摘要 V Abstract VI 縮寫表 (Abbreviations) VIII 第一章、緒論 (Introduction) 1 1.1細胞再編程 (Cell reprogramming) 1 1.2誘導性多能幹細胞Induced Pluripotenct Stem Cells (iPSCs) 2 1.2.1 OSKM轉錄因子的生理作用，及在iPSCs中的重要性 3 1.2.2 胚胎幹細胞轉錄網絡調控多能性 6 1.3多環芳香烴受體 (Aryl Hydrocarbon Receptor, AHR) 7 1.4研究動機 11 第二章、材料和方法 (Materials and methods) 13 2.1實驗材料 13 2.2實驗方法 14 2.2.1 CRISPR/Cas9 AHR-KO細胞建立 14 2.2.2人類肺腺癌上皮細胞株 (A549) 與AHR-KO細胞培養 15 2.2.3細胞存活率試驗 (Cell viability assay) 15 2.2.4西方墨點法 (Western blot analysis) 15 2.2.5反轉錄聚合酶連鎖反應 (Reverse transcription-polymerase chain reaction, RT-PCR) 17 2.2.6細胞傷口癒合法 (Wound healing assay) 18 2.2.7細胞免疫螢光染色法 (Immunofluorescence staining) 19 2.2.8 細胞球狀試驗 ( Cell spheroid assay) 19 2.2.9 統計分析 (Statistic analysis) 20 3.1 CRISPR/Cas9 系統建立的AHR-KO 細胞的確效與細胞型態變化 21 3.2 AHR基因剔除後細胞生長速率下降 21 3.3 AHR基因剔除後細胞重啟多能特性 21 3.4 AHR基因剔除促進細胞表現多能性轉錄因子 22 3.5 AHR基因剔除後細胞移行能力下降 23 3.6 AHR基因剔除後，Smad2及磷酸化態Smad2增加、Smad3及磷酸化態Smad3表現量減少 23 3.7 AHR基因剔除後細胞具有抗纖維化的特性 25 3.8 AHR基因剔除後EMT基因表現 26 第四章、討論 (Discussion) 27 4.1 AHR對於多能分化性之影響 27 4.2 AHR在TGF/Smad纖維化進程中扮演的角色 28 4.3 AHR跟Cell reprogramming 調控的幹性 (Stemness) 探討 31 4.4本實驗AHR-KO細胞與傳統iPSC的特質差異 35 第五章、結論 (Conclusion) 40 參考文獻 (Reference) 42 圖表 (Figures and Tables) 59 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討AHR-KO 促使A549細胞再編程具有抗纖維化效果的作用機制 | zh_TW |
| dc.title | The Mechanism Involving AHR-KO Drove Cell Reprogramming, and Associated Ameliorating Effects on Fibrogenesis in A549 Cell Line | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 109-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 劉秉慧(Biing-Hui Liu) | |
| dc.contributor.oralexamcommittee | 李青澔(Ching-Hao Li) | |
| dc.subject.keyword | 多環芳香烴受體,CRISPR/Cas9,誘導性多能幹細胞,多能性,TGF-b1/Smad,纖維化, | zh_TW |
| dc.subject.keyword | Aryl hydrocarbon receptor (AHR),CRISPR/Cas9,iPSCs,pluripotency,TGF-b1/Smad,fibrosis, | en |
| dc.relation.page | 75 | |
| dc.identifier.doi | 10.6342/NTU202100247 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2021-02-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2901202111101400.pdf 目前未授權公開取用 | 2.96 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。