請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66937
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李心予 | |
dc.contributor.author | Ya-Chi Chang | en |
dc.contributor.author | 張雅琪 | zh_TW |
dc.date.accessioned | 2021-06-17T01:15:16Z | - |
dc.date.available | 2022-08-24 | |
dc.date.copyright | 2017-08-24 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-14 | |
dc.identifier.citation | 1. Mikkola, H.K. and S.H. Orkin, The journey of developing hematopoietic stem cells. Development, 2006. 133(19): p. 3733-44.
2. Cumano, A. and I. Godin, Ontogeny of the hematopoietic system. Annu Rev Immunol, 2007. 25: p. 745-85. 3. Chiyo Mizuochi, S.T.F., Katia Biasch, Yuka Horio, Yoshikane Kikushige, Kenzaburo Tani, and M.T. Koichi Akashi, Daisuke Sugiyama, Intra-Aortic Clusters Undergo Endothelial to Hematopoietic Phenotypic Transition during Early Embryogenesis. PLoS One, 2012. 4. Chiyo Mizuochi, S.T.F., Katia Biasch, Yuka Horio, Yoshikane Kikushige, Kenzaburo Tani, and M.T. Koichi Akashi, Daisuke Sugiyama, Intra-Aortic Clusters Undergo Endothelial to Hematopoietic Phenotypic Transition during Early Embryogenesis. PLoS One, 2012. 7: p. e35763. 5. Murayama, E., et al., Tracing hematopoietic precursor migration to successive hematopoietic organs during zebrafish development. Immunity, 2006. 25(6): p. 963-75. 6. Didier Y. R. Stainier, et al., cloche, an early acting zebrafish gene, is required by both the endothelial and hematopoietic lineages. Development: p. 3141-3150. 7. Vogeli, K.M., et al., A common progenitor for haematopoietic and endothelial lineages in the zebrafish gastrula. Nature, 2006. 443(7109): p. 337-9. 8. Bertrand, J.Y., et al., Haematopoietic stem cells derive directly from aortic endothelium during development. Nature, 2010. 464(7285): p. 108-11. 9. Kissa, K. and P. Herbomel, Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature, 2010. 464(7285): p. 112-5. 10. Jin, H., J. Xu, and Z. Wen, Migratory path of definitive hematopoietic stem/progenitor cells during zebrafish development. Blood, 2007. 109(12): p. 5208-14. 11. Chen, A.T. and L.I. Zon, Zebrafish blood stem cells. J Cell Biochem, 2009. 108(1): p. 35-42. 12. Umezu-Goto, M., et al., Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol, 2002. 158(2): p. 227-33. 13. van Meeteren, L.A., et al., Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol, 2006. 26(13): p. 5015-22. 14. Choi, J.W., et al., LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol, 2010. 50: p. 157-86. 15. Pebay, A., C.S. Bonder, and S.M. Pitson, Stem cell regulation by lysophospholipids. Prostaglandins Other Lipid Mediat, 2007. 84(3-4): p. 83-97. 16. Mirella Dottori, J.L., Ann M. Turnley, Alice Pébay Ph.D., Lysophosphatidic Acid Inhibits Neuronal Differentiation of Neural Stem/Progenitor Cells Derived from Human Embryonic Stem Cells. Stem Cells, 2008: p. 1146-1154. 17. Liu, Y.B., et al., LPA induces osteoblast differentiation through interplay of two receptors: LPA1 and LPA4. J Cell Biochem, 2010. 109(4): p. 794-800. 18. Li, H., et al., Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis. EMBO J, 2014. 33(12): p. 1383-96. 19. Evseenko, D., et al., Lysophosphatidic acid mediates myeloid differentiation within the human bone marrow microenvironment. PLoS One, 2013. 8(5): p. e63718. 20. Igarashi, H., et al., The lysophosphatidic acid receptor LPA4 regulates hematopoiesis-supporting activity of bone marrow stromal cells. Sci Rep, 2015. 5: p. 11410. 21. Chiang, C.L., et al., Lysophosphatidic acid induces erythropoiesis through activating lysophosphatidic acid receptor 3. Stem Cells, 2011. 29(11): p. 1763-73. 22. Lin, K.H., et al., Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis. Sci Rep, 2016. 6: p. 27050. 23. Jason Ear, H.H., Tianna Wilson, Zahra Tehrani, Anne Lindgren, Victoria Sung, Abderrahmane Laadem, Thomas O. Daniel, Rajesh Chopra and Shuo Lin, RAP-011 improves erythropoiesis in zebrafish model of Diamond-Blackfan anemia through antagonizing lefty1. Blood, 2015. 126: p. 880-890. 24. Jensen, F.B., Nitric oxide formation from nitrite in zebrafish. J Exp Biol, 2007. 210(Pt 19): p. 3387-94. 25. Kasem Kulkeaw, D.S., Zebrafish erythropoiesis and the utility of fish as model of anemia. Stem Cell Research % Therapy, 2012. 3: p. 55. 26. Zhu, H., et al., Regulation of the lmo2 promoter during hematopoietic and vascular development in zebrafish. Dev Biol, 2005. 281(2): p. 256-69. 27. Gering, M. and R. Patient, Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell, 2005. 8(3): p. 389-400. 28. Calbet, J.A., et al., Importance of hemoglobin concentration to exercise: acute manipulations. Respir Physiol Neurobiol, 2006. 151(2-3): p. 132-40. 29. Kolb, E.M., et al., Erythropoietin elevates VO2,max but not voluntary wheel running in mice. J Exp Biol, 2010. 213(3): p. 510-9. 30. Abdallah, S.J., B.S. Thomas, and M.G. Jonz, Aquatic surface respiration and swimming behaviour in adult and developing zebrafish exposed to hypoxia. J Exp Biol, 2015. 218(Pt 11): p. 1777-86. 31. Kasem Kulkeaw, D.S., Zebrafish erythropoiesis and the utility of fish as model of anemia. 2012. 32. Traver, D., et al., Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nat Immunol, 2003. 4(12): p. 1238-46. 33. Ho, Y.H., et al., Opposing regulation of megakaryopoiesis by LPA receptors 2 and 3 in K562 human erythroleukemia cells. Biochim Biophys Acta, 2015. 1851(2): p. 172-83. 34. Rossi, A., et al., Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature, 2015. 524(7564): p. 230-3. 35. Lin, M.J. and S.J. Lee, Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae. Sci Rep, 2016. 6: p. 36188. 36. Kok, F.O., et al., Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish. Dev Cell, 2015. 32(1): p. 97-108. 37. Erslev, A.J. and A. Besarab, Erythropoietin in the pathogenesis and treatment of the anemia of chronic renal failure. Kidney International, 1997. 51(3): p. 622-630. 38. Wojchowski, D.M., P. Sathyanarayana, and A. Dev, Erythropoietin receptor response circuits. Curr Opin Hematol, 2010. 17(3): p. 169-76. 39. Fukushima, N., et al., Comparative analyses of lysophosphatidic acid receptor-mediated signaling. Cell Mol Life Sci, 2015. 72(12): p. 2377-94. 40. James F. Amatruda, a.L.I.Z., Dissecting Hematopoiesis and Disease Using the Zebrafish. Developmental Biology, 2005: p. 1–15. 41. Diep, C.Q., et al., Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature, 2011. 470(7332): p. 95-100. 42. Stachura, D.L., et al., Zebrafish kidney stromal cell lines support multilineage hematopoiesis. Blood, 2009. 114(2): p. 279-89. 43. Knowlden, S. and S.N. Georas, The autotaxin-LPA axis emerges as a novel regulator of lymphocyte homing and inflammation. J Immunol, 2014. 192(3): p. 851-7. 44. Zhao, C., et al., TNF-alpha promotes LPA1- and LPA3-mediated recruitment of leukocytes in vivo through CXCR2 ligand chemokines. J Lipid Res, 2011. 52(7): p. 1307-18. 45. CE Willett, J.C., LA Steiner, Characterization and expression of the recombination activating genes (rag1 and rag2) of zebrafish. Immunogenetics, 1997: p. 394-404. 46. Tang, Q., et al., Optimized cell transplantation using adult rag2 mutant zebrafish. Nat Methods, 2014. 11(8): p. 821-4. 47. Moore, J.C., et al., Single-cell imaging of normal and malignant cell engraftment into optically clear prkdc-null SCID zebrafish. J Exp Med, 2016. 213(12): p. 2575-2589. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66937 | - |
dc.description.abstract | 造血功能是造血幹細胞進一步分化成特定血球族群的動態過程。目前已知水解磷酸酯受器3 (Lysophosphatidic acid receptor 3, LPA3) 參與造血幹細胞與骨髓微環境的調控。本實驗室先前的研究發現,在人類造血幹細胞與斑馬魚生物模式中,活化 LPA3 會提高紅血球生成素 (EPO) 誘導的紅血球生成。此外,在斑馬魚中利用核酸類似物 (morpholino, MO) 降低 LPA3 會導致紅血球生成的缺失。然而藥物刺激或是化學物引發的基因調控有可能引發額外的未知影響。因此,本研究希望在斑馬魚上使用基因剔除 (Knock-out) 的技術探討 LPA3 於造血功能中扮演的角色。本次研究中,我們使用 transcription activator-like (TAL) effector nucleases (TALEN) 在 LPA3 基因組的第一段內插子中踢除兩個鹼基對,建構出 LPA3 基因缺失的斑馬魚。和野生型基因相比之下,LPA3 踢除的胚胎所含的血紅素與游動能力並沒有顯著的差異。然而,在受精後的三天內的胚胎中,造血相關的基因表現出現了延遲的現象,顯示 LPA3 可能在斑馬魚胚胎發育中影響了造血的功能。此外,在 LPA3 基因踢除的成魚中,其造血中樞 - 全腎骨髓的面積縮小,且全腎骨髓中的血球細胞族群比例也產生變化。綜觀諸多結果顯示 LPA3 在斑馬魚的胚胎或成體時期的造血功能中都扮演很重要的角色。 | zh_TW |
dc.description.abstract | Hematopoiesis is a dynamic process by which hematopoietic stem cells (HSCs) differentiate into the specific blood cell lineages. Lysophosphatidic acid (LPA) receptors have been shown to be involved in the regulation of hematopoiesis in HSCs and bone marrow microenvironment. In our previous studies, we demonstrated that activation of LPA receptor 3 (LPA3) promotes erythropoietin(EPO)-dependent erythropoiesis in HSCs and zebrafish. Moreover, knockdown of Lpa3 expression by using morpholino (MO) caused erythropoietic defects in zebrafish embryos. However, the pharmacological activation and chemical-dependent gene-depletion of LPA3 may have redundant effects during the development of zebrafish. Therefore, we aim to generate Lpa3 knockout zebrafish to clarify the roles of Lpa3 in hematopoiesis. In this study, we established LPA3 knockout (Lpa3-/-) zebrafish by deleting 2 base pairs in exon 1 using transcription activator-like effector nucleases (TALEN). As expected, the expressions of early hematopoietic markers are delayed in Lpa3-/- embryos within 3 days post fertilization (dpf) by real-time PCR, implying that Lpa3 is involved in the embryonic hematopoiesis in zebrafish. However, 5 dpf Lpa3-/- larvae showed no deficiency in the amount of hemoglobin and locomotor activities by histochemistry staining and high-throughput behavioral studies, respectively. Interestingly, adult Lpa3-/- zebrafish showed smaller whole kidney marrow (WKM) in histological analysis compared to the wild type. Flow cytometry analysis also showed the decreased population of precursors and lymphocytes in adult Lpa3-/- zebrafish, suggesting that Lpa3 may involve in the lymphopoiesis of zebrafish. Taken together, these findings reveal critical roles of Lpa3 in the embryonic development and adult hematopoiesis in zebrafish. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:15:16Z (GMT). No. of bitstreams: 1 ntu-106-R04b21011-1.pdf: 4507338 bytes, checksum: 670e1f4855d67d0ec369310ce19871dd (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 致謝.....................................................................................................................................................ii
中文摘要...........................................................................................................................................iii Abstract...........................................................................................................................iv Contents..........................................................................................................................vi 1 Introduction..................................................................................................................1 1.1 Hematopoiesis .........................................................................................................1 1.2 Hematopoiesis in zebrafish......................................................................................1 1.3 The functions of lysophosphatidic acid...................................................................2 1.4 Relationship between LPA and hematopoiesis........................................................3 1.5 Functional roles of LPA3 in hematopoiesis.............................................................3 2 Materials and Methods...............................................................................................5 2.1 Zebrafish maintenance and embryo collection.......................................................5 2.2 Knock-out zebrafish line establishment..................................................................5 2.3 mRNA extraction....................................................................................................5 2.4 Reverse-transcription and Quantitative real-time PCR...........................................6 2.5 Pharmacological treatment......................................................................................7 2.6 O-dianisidine staining..............................................................................................7 2.7 Peripheral blood collection and hemoglobin absorption.........................................7 2.8 Cell collection from whole kidney marrow.............................................................8 2.9 Flow cytometry........................................................................................................8 2.10 Locomotion teaching and analysis.........................................................................8 2.11 Histology................................................................................................................9 2.12 Statistical Analysis.................................................................................................9 3 Results.........................................................................................................................10 3.1 Generation of Lpa3-/- zebrafish by TALEN gene knockout system.......................10 3.2 Lpa3-/- embryos exist developmental delay in primitive hematopoiesis...............11 3.3 Lpa3-/- larvae show no erythropoietic defect and weak response to Lpa3 agonist 2S-OMPT.............................................................................................................................12 3.4 Locomotor is not affected in Lpa3-/- larvae............................................................12 3.5 Adult Lpa3-/- does not show erythropoietic defect..................................................13 3.6 The morphological change of WKM in adult Lpa3-/- zebrafish..............................13 3.7 Lpa3-/- have decreased numbers of hematopoietic precursors and lymphocytes in adult WKM ....................................................................................................................14 4 Conclusions and Discussions....................................................................................15 5 Reference....................................................................................................................19 6 Figures........................................................................................................................23 | |
dc.language.iso | en | |
dc.title | 水解磷酸酯受器3於斑馬魚的造血功能中扮演之角色 | zh_TW |
dc.title | The Roles of Lysophosphatidic Acid Receptor 3 in Hematopoiesis of Zebrafish | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 姚少凌,張百恩,蕭崇德 | |
dc.subject.keyword | 水解磷酸酯受器3,斑馬魚,造血功能,紅血球生成, | zh_TW |
dc.subject.keyword | Lysophosphatidic acid receptor 3 (Lpa3),zebrafish,hematopoiesis,erythropoiesis, | en |
dc.relation.page | 36 | |
dc.identifier.doi | 10.6342/NTU201702592 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-15 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生命科學系 | zh_TW |
顯示於系所單位: | 生命科學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-1.pdf 目前未授權公開取用 | 4.4 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。