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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李建國(Chien-Kuo Lee) | |
| dc.contributor.author | Jui-Tse Weng | en |
| dc.contributor.author | 翁瑞澤 | zh_TW |
| dc.date.accessioned | 2021-06-17T02:18:31Z | - |
| dc.date.available | 2022-09-08 | |
| dc.date.copyright | 2017-09-08 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-22 | |
| dc.identifier.citation | Belz, G.T., and Nutt, S.L. (2012). Transcriptional programming of the dendritic cell network. Nat Rev Immunol 12, 101-113.
Bettini, M., Xi, H., Milbrandt, J., and Kersh, G.J. (2002). Thymocyte Development in Early Growth Response Gene 1-Deficient Mice. The Journal of Immunology 169, 1713-1720. Bouchard, F., Belanger, S.D., Biron-Pain, K., and St-Pierre, Y. (2010). EGR-1 activation by EGF inhibits MMP-9 expression and lymphoma growth. Blood 116, 759-766. Carter, J.H., and Tourtellotte, W.G. (2007). Early growth response transcriptional regulators are dispensable for macrophage differentiation. J Immunol 178, 3038-3047. Caton, M.L., Smith-Raska, M.R., and Reizis, B. (2007). Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. J Exp Med 204, 1653-1664. Chen, Y.L., Chen, T.T., Pai, L.M., Wesoly, J., Bluyssen, H.A., and Lee, C.K. (2013). A type I IFN-Flt3 ligand axis augments plasmacytoid dendritic cell development from common lymphoid progenitors. J Exp Med 210, 2515-2522. Clarke, E., Rahman, N., Page, N., Rolph, M.S., Stewart, G.J., and Jones, G.J. (2008). Functional characterization of the atopy-associated gene PHF11. J Allergy Clin Immunol 121, 1148-1154.e1143. Colonna, M., Trinchieri, G., and Liu, Y.J. (2004). Plasmacytoid dendritic cells in immunity. Nat Immunol 5, 1219-1226. Crowley, M., Inaba, K., Witmer-Pack, M., and Steinman, R.M. (1989). The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. Cell Immunol 118, 108-125. Crozat, K., Tamoutounour, S., Vu Manh, T.P., Fossum, E., Luche, H., Ardouin, L., Guilliams, M., Azukizawa, H., Bogen, B., Malissen, B., et al. (2011). Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8alpha+ type. J Immunol 187, 4411-4415. Friedman, A.D. (2002). Transcriptional regulation of myelopoiesis. International journal of hematology 75, 466-472. Gashler, A., and Sukhatme, V.P. (1995). Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Progress in nucleic acid research and molecular biology 50, 191-224. Godec, J., Tan, Y., Liberzon, A., Tamayo, P., Bhattacharya, S., Butte, A.J., Mesirov, J.P., and Haining, W.N. (2016). Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation. Immunity 44, 194-206. Gomard, T., Michaud, H.A., Tempe, D., Thiolon, K., Pelegrin, M., and Piechaczyk, M. (2010). An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. PLoS One 5, e9585. Gururajan, M., Simmons, A., Dasu, T., Spear, B.T., Calulot, C., Robertson, D.A., Wiest, D.L., Monroe, J.G., and Bondada, S. (2008). Early growth response genes regulate B cell development, proliferation and immune response. Journal of immunology (Baltimore, Md. : 1950) 181, 4590-4602. Heng, T.S., and Painter, M.W. (2008). The Immunological Genome Project: networks of gene expression in immune cells. Nat Immunol 9, 1091-1094. Ichikawa, E., Hida, S., Omatsu, Y., Shimoyama, S., Takahara, K., Miyagawa, S., Inaba, K., and Taki, S. (2004). Defective development of splenic and epidermal CD4+ dendritic cells in mice deficient for IFN regulatory factor-2. Proc Natl Acad Sci U S A 101, 3909-3914. Ikari, J., Inamine, A., Yamamoto, T., Watanabe-Takano, H., Yoshida, N., Fujimura, L., Taniguchi, T., Sakamoto, A., Hatano, M., Tatsumi, K., et al. (2014). Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells. Allergy 69, 223-230. Kee, B.L. (2009). E and ID proteins branch out. Nat Rev Immunol 9, 175-184. Kumbrink, J., Kirsch, K.H., and Johnson, J.P. (2010). EGR1, EGR2, and EGR3 activate the expression of their coregulator NAB2 establishing a negative feedback loop in cells of neuroectodermal and epithelial origin. J Cell Biochem 111, 207-217. Laouar, Y., Welte, T., Fu, X.-Y., and Flavell, R.A. (2003). STAT3 Is Required for Flt3L-Dependent Dendritic Cell Differentiation. Immunity 19, 903-912. Laslo, P., Spooner, C.J., Warmflash, A., Lancki, D.W., Lee, H.J., Sciammas, R., Gantner, B.N., Dinner, A.R., and Singh, H. (2006). Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell 126, 755-766. Lewis, K.L., Caton, M.L., Bogunovic, M., Greter, M., Grajkowska, L.T., Ng, D., Klinakis, A., Charo, I.F., Jung, S., Gommerman, J.L., et al. (2011). Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity 35, 780-791. Lin, Q., Chauvistre, H., Costa, I.G., Gusmao, E.G., Mitzka, S., Hanzelmann, S., Baying, B., Klisch, T., Moriggl, R., Hennuy, B., et al. (2015). Epigenetic program and transcription factor circuitry of dendritic cell development. Nucleic Acids Res 43, 9680-9693. Mager, G.M., Ward, R.M., Srinivasan, R., Jang, S.W., Wrabetz, L., and Svaren, J. (2008). Active gene repression by the Egr2.NAB complex during peripheral nerve myelination. J Biol Chem 283, 18187-18197. Miah, M.A., Byeon, S.E., Ahmed, M.S., Yoon, C.H., Ha, S.J., and Bae, Y.S. (2013). Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity. Eur J Immunol 43, 2484-2496. Miao, T., Symonds, A.L.J., Singh, R., Symonds, J.D., Ogbe, A., Omodho, B., Zhu, B., Li, S., and Wang, P. (2017). Egr2 and 3 control adaptive immune responses by temporally uncoupling expansion from T cell differentiation. The Journal of Experimental Medicine. Milbrandt, J. (1987). A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science 238, 797-799. Mildner, A., and Jung, S. (2014). Development and function of dendritic cell subsets. Immunity 40, 642-656. Min, I.M., Pietramaggiori, G., Kim, F.S., Passegue, E., Stevenson, K.E., and Wagers, A.J. (2008). The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell 2, 380-391. Musselman, C.A., and Kutateladze, T.G. (2009). PHD Fingers: Epigenetic Effectors and Potential Drug Targets. Molecular Interventions 9, 314-323. Redecke, V., Wu, R., Zhou, J., Finkelstein, D., Chaturvedi, V., High, A.A., and Häcker, H. (2013). Generation of hematopoietic progenitor cell lines with myeloid and lymphoid potential. Nature methods 10, 795-803. Schiavone, D., Avalle, L., Dewilde, S., and Poli, V. (2011). The immediate early genes Fos and Egr1 become STAT1 transcriptional targets in the absence of STAT3. FEBS letters 585, 2455-2460. Schliehe, C., Flynn, E.K., Vilagos, B., Richson, U., Swaminathan, S., Bosnjak, B., Bauer, L., Kandasamy, R.K., Griesshammer, I.M., Kosack, L., et al. (2015). The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection. Nat Immunol 16, 67-74. Schmitt, H., Sell, S., Koch, J., Seefried, M., Sonnewald, S., Daniel, C., Winkler, T.H., and Nitschke, L. (2016). Siglec-H protects from virus-triggered severe systemic autoimmunity. J Exp Med 213, 1627-1644. Seiler, M.P., Mathew, R., Liszewski, M.K., Spooner, C., Barr, K., Meng, F., Singh, H., and Bendelac, A. (2012). Elevated and sustained Egr1 and Egr2 expression controls NKT lineage differentiation in response to TCR signaling. Nature immunology 13, 264-271. Seyfert, V.L., Sukhatme, V.P., and Monroe, J.G. (1989). Differential expression of a zinc finger-encoding gene in response to positive versus negative signaling through receptor immunoglobulin in murine B lymphocytes. Molecular and Cellular Biology 9, 2083-2088. Siegal, F.P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P.A., Shah, K., Ho, S., Antonenko, S., and Liu, Y.J. (1999). The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 1835-1837. Steinman, R.M., and Cohn, Z.A. (1973). Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137, 1142-1162. Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., and Mesirov, J.P. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102, 15545-15550. Suzuki, S., Honma, K., Matsuyama, T., Suzuki, K., Toriyama, K., Akitoyo, I., Yamamoto, K., Suematsu, T., Nakamura, M., Yui, K., and Kumatori, A. (2004). Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha- dendritic cell development. Proc Natl Acad Sci U S A 101, 8981-8986. Swirnoff, A.H., and Milbrandt, J. (1995). DNA-binding specificity of NGFI-A and related zinc finger transcription factors. Mol Cell Biol 15, 2275-2287. Thiel, G., and Cibelli, G. (2002). Regulation of life and death by the zinc finger transcription factor Egr-1. J Cell Physiol 193, 287-292. Wu, L., D'Amico, A., Winkel, K.D., Suter, M., Lo, D., and Shortman, K. (1998). RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity 9, 839-847. Zhang, Y., Dean, C., Chessum, L., Nguyen, D., Stewart, M., Taylor, M., Cookson, W.O., and Moffatt, M.F. (2014). Functional analysis of a novel ENU-induced PHD finger 11 (Phf11) mouse mutant. Mammalian genome : official journal of the International Mammalian Genome Society 25, 573-582. Zhang, Y., Leaves, N.I., Anderson, G.G., Ponting, C.P., Broxholme, J., Holt, R., Edser, P., Bhattacharyya, S., Dunham, A., Adcock, I.M., et al. (2003). Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nature genetics 34, 181-186. Zhu, X., Lin, Y., Bacanamwo, M., Chang, L., Chai, R., Massud, I., Zhang, J., Garcia-Barrio, M.T., Thompson, W.E., and Chen, Y.E. (2007). Interleukin-1 beta-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells. Cardiovascular research 76, 141-148. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68354 | - |
| dc.description.abstract | 樹突細胞對於抗原呈現以及連結先天及後天免疫十分重要。樹突細胞主要可 以分為漿狀樹突細胞以及傳統樹突細胞。兩者產生的比例有其相對性。由於擁有非 常短的生命週期，兩者皆得持續的從骨髓系統及淋巴系統的造血前驅細胞補充。先 前的研究已經知道在Flt3 配體 (Flt3 ligand, FL)的刺激下，共同淋巴前驅細胞 (common lymphoid progenitors, CLP) 和共同髓原前驅細胞(common myeloid progneitors, CMP)可以分化出漿狀樹突細胞。然而，漿狀樹突細胞發育的分子調控 機制到目前還不十分清楚。因此，在透過基因富集分析方法(GSEA)以及基因微陣 列之比較，我們篩選到一些轉錄因子在傳統樹突細胞中具有較高的表現量且從未 被報導過參與樹突細胞的發育。在利用基因靜默(knockdown)技術降低這些轉錄因 子在iHSPC 中的表現後，在FL 的刺激下，分析其漿狀樹突細胞分化的情形，我們 發現一系列的轉錄因子能降低漿狀樹突細胞的產生。其中以Egr1 和Phf11 這兩個 分子最令人感興趣。其中，Egr1 已經被報導參與在其他免疫細胞的分化。然而， 從未有研究指出Egr1 在樹突細胞的發育扮演腳色。進一步發現在iHSPC 中，Egr1 可以被FL 刺激而迅速表現並可能透過結合啟動子的方式，調控轉錄因子Id2 的表 現，進而影響樹突細胞的分化。最重要的是，分析Egr1 基因剔除鼠後發現pDC 的 比例及數量都有顯著的下降，而其他免疫細胞則不受到影響。最後，利用Egr1 基 因剔除的小鼠骨髓經FL 刺激培養後，pDC 和cDC1 的比例也有顯著的減少，證明了Egr1 的基因剔除是在細胞內部造成pDC 的分化受到影響。總結以上，Egr1 可 能在樹突細胞的發育中扮演從未被報導過的調控角色。 | zh_TW |
| dc.description.abstract | Dendritic cells (DCs) are critical for antigen presentation and can link the innate immunity and the adaptive immunity. DCs including conventional DCs (cDCs) and plasmacytoid DCs (pDCs). Because of the short life span , they are constantly replenished from hematopoietic stem and progenitor cells (HSPC). Previously, we have shown that upon stimulation with Flt3 ligand (FL), common myeloid progenitor (CMPs) and common lymphoid progenitors (CLPs) have the potential to develop pDC at steady-state. However, the molecular mechanism of DC development from these progenitors is still unclear. Therefore, through differential expression analysis and gene set enrichment analysis (GSEA), we have identified several transcription factors (TFs) that are preferentially expression in cDC versus pDC. Using knockdown technology in an immortalized HSPC (iHSPC) line and in vitro differentiation system with FL, we have analyzed the effect of RNA silencing of TF of interests on cDC and pDC development. We found several TFs that were capable of decreasing pDC potential, including early growth response 1 (Egr1) and Phf11. Egr1 is known for determining the differentiation pathway of myeloid cell precursors. However, the role of Egr1 in DC development has not been reported before. Our preliminary data showed that Egr1 was an FL- inducible gene in iHSPC. Egr1 knockdown in iHSPC decreased pDC while increased CD11b-B220double negative (DN) population in a feeder-free system. Interestingly, Egr1 may bind to the promoter of Id2, a master regulator for cDC development. Most importantly, the frequency of pDC were decreased in Egr1 knockout mice while other immune cell population including cDC were not affected. Moreover, pDC and cDC1 also were deceased daily in vitro BM culture suggesting that there is an intrinsic requirement of Egr1 for pDC development. Together, Egr1 may represent a novel TF regulating DC development. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T02:18:31Z (GMT). No. of bitstreams: 1 ntu-106-R04449012-1.pdf: 9119025 bytes, checksum: 0402ffd7498dab725b2ab4e976d20df4 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | Table of contents
誌謝 i 中文摘要 ii Abstract iv Abbreviation vi Table of contents viii Chapter I Introduction - 1 - 1.1 Dendritic cell subsets - 2 - 1.2 Dendritic cell development and transcription factors regulation. - 3 - 1.3 Gene set enrichment analysis - 4 - 1.4 Plant homeodomain finger protein 11 - 5 - 1.5 Early growth response 1 - 6 - 1.6 Rationale - 7 - 1.7 Aims - 7 - Chapter II Materials and Methods - 8 - 2.1 Mice - 9 - 2.2 Flow cytometry and primary cell sorting - 9 - 2.3 Table 1. List of antibodies - 9 - 2.4 Quantitative RT-PCR - 11 - 2.5 Table 2. List of primer sequences (5’—3’) - 11 - 2.6 In vitro culture and differrntiation of iHSPC - 12 - 2.7 Recombinant FL preparation - 12 - 2.8 Generation of iHSPC cell line - 13 - 2.9 Generation of iHSPC stably transduced shRNA - 14 - 2.10 Adoptive transfer - 14 - Chapter III Results - 15 - 3.1 Screening of transcription factors in cDCs development - 16 - 3.2 Phf11 knockdown in iHSPC decreases pDC development - 17 - 3.3 Expression of DC-specific transcription factors in shPhf11 iHSPC - 18 - 3.4 Phf11 knockdown in iHSPC decreases pDC production in MS-5 feeder culture system. - 18 - 3.5 Egr1 knockdown in iHSPC decreases pDC production from iHSPC - 19 - 3.6 Egr1 knockout in iHSPC decreases pDC production in vitro - 19 - 3.7 Development of pDC and not cDC is impaired in Egr1 KO mice - 20 - 3.8 Egr1-deficient does not affect the development of other immune cells - 21 - 3.9 The development of pDC from CDP or CLP of Egr1 deficiency mice is not impaired - 22 - 3.10 pDC development from Egr1 KO BM cells is impaired - 23 - 3.11 The developmental defect of pDC from Egr1 KO BM cells is not rescued by high-dose FL treatment - 23 - 3.12 The cDC and pDC development is not impaired in the chimeric mice adoptively transferred with Egr1-/-BM - 24 - 3.13 The frequency of T cell is decreased in the chimeric mice adoptively transferred with Egr1-/-BM - 25 - 3.14 FL induces Egr1 production in the early phase of DC differentiation. - 25 - 3.15 EGR1 binds and regulates Id2-driven reporter activity - 26 - Chapter IV Discussion - 28 - 4.1 GSEA, a powerful tool for screening genes in the same pathways - 29 - 4.2 Phf11 is a potential transcription factor regulating DC development - 30 - 4.3 Egr1 is a potential transcription factor for pDC development - 31 - 4.4 Egr1 may regulate pDC development in cell intrinsic effect - 31 - 4.5 Egr1 may participate cDC1 development by regulating Irf-2 expression in vitro - 32 - 4.6 Egr proteins are inducible and regulate Id2 expression in FL-dependent manner - 32 - 4.7 The role of other Egr proteins in DC development - 33 - 4.8 The hypothetic model of the Egr1-regulated mechanism in DC development in the BM. - 34 - Chapter V Figures - 35 - Figure 1. Screening of transcription factors that may be involved in DCs development. - 37 - Figure 2. Phf11 knockdown in iHSPC decreases pDC potential in vitro. - 39 - Figure 3. Expression of DC-specific transcription factors in shPhf11 iHSPC. - 40 - Figure 4. Phf11 knockdown in iHSPC decreases pDC production in MS-5 feeder culture system. - 41 - Figure 5. Egr1 knockdown in iHSPC decreases pDC production and increases double negative population. - 42 - Figure 6. Egr1 knockout in iHSPC decreases pDC production. - 43 - Figure 7. The frequency of cDC is not affected in Egr1 KO mice. - 45 - Figure 8. The frequency of pDC is decreased in the bone marrow of Egr1KO mice. - 47 - Figure 9. The frequency of T, B, NK, NKT cell, macrophage and granulocyte is not affected in Egr1-/- mice. - 50 - Figure 10. The development of CDP/CLP-derived pDC from Egr1 deficiency mice are not impaired. - 53 - Figure 11. Reduced pDC development and altered cell number and ratio of cDC1/cDC2 in the absence of Egr1. - 56 - Figure 12. The developmental impairment of pDC from Egr1-/- BM cells cannot be rescued by high-dose of FL. - 59 - Figure 13. The frequency of pDC is not decreased in the chimeric mice adoptively transferred with Egr1-/-BM - 62 - Figure 14. The frequency of cDC is not affected in the chimeric mice adoptively transferred with Egr1-/- BM. - 65 - Figure 15. The frequency of T cell is decreased in the chimeric mice adoptively transferred with Egr1-/- BM. - 68 - Figure 16. FL transiently induces Egr1 expression in iHSPC. - 70 - Figure 17. Egr1 binds and regulates Id2-driven reporter activity. - 71 - Figure 18. The hypothetic model of the Egr1-regulated mechanism for DC development in the BM. - 73 - Chapter VI References - 74 - | |
| dc.language.iso | en | |
| dc.subject | 共同淋巴前驅細胞 | zh_TW |
| dc.subject | 基因富集分析方法 | zh_TW |
| dc.subject | 漿狀樹突細胞發育 | zh_TW |
| dc.subject | 轉錄因子 | zh_TW |
| dc.subject | 共同髓原前驅細胞 | zh_TW |
| dc.subject | Egr1 | en |
| dc.subject | Phf11 | en |
| dc.subject | Plasmacytoid Dendritic Cell Development | en |
| dc.subject | Flt3 Ligand | en |
| dc.subject | GSEA | en |
| dc.title | 轉錄因子Phf11 和Egr1 在漿狀樹突細胞發育中的調控 | zh_TW |
| dc.title | Regulation of Plasmacytoid Dendritic Cell Development by Two
Transcription Factors Phf11 and Egr1 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林國儀(Kuo-I Lin),嚴仲陽(Jeffrey Yen) | |
| dc.subject.keyword | 漿狀樹突細胞發育,轉錄因子,共同淋巴前驅細胞,共同髓原前驅細胞,基因富集分析方法, | zh_TW |
| dc.subject.keyword | Egr1,Phf11,Plasmacytoid Dendritic Cell Development,Flt3 Ligand,GSEA, | en |
| dc.relation.page | 82 | |
| dc.identifier.doi | 10.6342/NTU201703101 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-22 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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