诱导多能干细胞技术在猪转基因研究中的应用前景

摘要/Abstract

摘要： 长期以来,猪都是科学研究中重要的生物模型,转基因猪在生物模型、器官移植和动物良种繁育等方面有着极其重要的研究及应用价值,而现在的转基因克隆猪的成功率及成活率都普遍偏低。诱导多能干细胞技术在再生医学和畜牧业等领域有着广泛而诱人的应用前景,但目前还较少被应用于转基因猪的研究中。作者对转基因技术和诱导多能干细胞技术的发展历程,特别是诱导多能干细胞技术在猪转基因研究中的应用进行简述,以期为开展相关研究的科研人员提供一定的参考。

关键词: 诱导多能干细胞; 猪; 转基因; 生物模型

Abstract: Pig has been an important biologic model of scientific research over the years. Transgenic pigs also have extremely important effects in biologic model, organ transplantation, animal breed breeding, and so on. There are several problems for the transgenic cloned pigs, such as low successful rate and live rate. The induced pluripotent stem cells (iPSCs) technology has wide and amazing application in regenerative medicine and animal husbandry while this technology has not deeply used in pig transgenic research. Here, we briefly review the transgenic technology, iPSCs technology, and the application of the iPSCs technology in the researches of transgenic cloned pigs for providing some references for researchers working in the fields.

Key words: induced pluripotent stem cells; pig; transgenic; biologic model

中图分类号:

S828

廖荣荣, 颉孝贤, 马育芳, 潘玉春. 诱导多能干细胞技术在猪转基因研究中的应用前景[J]. , 2013, 40(6): 90-95.

LIAO Rong-rong, XIE Xiao-xian, MA Yu-fang, PAN Yu-chun. The Application Prospect of Induced Pluripotent Stem Cells in Pig Transgenic Research[J]. , 2013, 40(6): 90-95.

参考文献

1 Bawden C S, Powell B C, Walker S K, et al. Expression of a wool intermediate filament keratin transgene in sheep fibre alters structure[J]. Transgenic Res,1998,7(4): 273~287.
2 Bibikova M, Beumer K, Trautman J K, et al. Enhancing gene targeting with designed zinc finger nucleases[J]. Science,2003,300(5620): 764.
3 Buehr M, Meek S, Blair K, et al. Capture of authentic embryonic stem cells from rat blastocysts[J]. Cell,2008,135(7): 1287~1298.
4 Chen L, Shiue Y, Bertolini L, et al. Establishment of pluripotent cell lines from porcine preimplantation embryos[J]. Theriogenology,1999,52(2): 195~212.
5 Cibelli J, Stice S, Kane J, et al. Production of germline chimeric bovine fetuses from transgenic embryonic stem cells[J]. Theriogenology,1997,47(1): 241.
6 Cibelli J B, Stice S L, Golueke P J, et al. Cloned transgenic calves produced from nonquiescent fetal fibroblasts[J]. Science,1998,280(5367): 1256~1258.
7 Clark A, Bessos H, Bishop J, et al. Expression of human anti-hemophilic factor IX in the milk of transgenic sheep[J]. Nat Biotechnol,1989,7(5): 487~492.
8 Dai Y, Vaught T D, Boone J, et al. Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs[J]. Nat Biotechnol,2002,20(3): 251~255.
9 Denning C, Priddle H. New frontiers in gene targeting and cloning: Success, application and challenges in domestic animals and human embryonic stem cells[J]. Reproduction,2003,126(1): 1~11.
10 Esteban M A, Xu J, Yang J, et al. Generation of induced pluripotent stem cell lines from Tibetan miniature pig[J]. J Biol Chem,2009,284(26): 17634~17640.
11 Evans M J, Kaufman M H. Establishment in culture of pluripotential cells from mouse embryos[J]. Nature,1981,292(5819): 154~156.
12 Ezashi T, Telugu B P, Alexenko A P, et al. Derivation of induced pluripotent stem cells from pig somatic cells[J]. Proc Natl Acad Sci,2009,106(27): 10993~10998.
13 Fraidenraich D, Stillwell E, Romero E, et al. Rescue of cardiac defects in ld knockout embryos by injection of embryonic stem cells[J]. Science,2004,306(5694): 247~252.
14 Gerfen R, Wheeler M. Isolation of embryonic cell-lines from porcine blastocysts[J]. Anim Biotechnol,1995,6(1): 1~14.
15 Golovan S P, Meidinger R G, Ajakaiye A, et al. Pigs expressing salivary phytase produce low-phosphorus manure[J]. Nat Biotechnol,2001,19(8): 741~745.
16 Gossler A, Doetschman T, Korn R, et al. Transgenesis by means of blastocyst-derived embryonic stem cell lines[J]. Proc Natl Acad Sci,1986,83(23): 9065.
17 Hammer R E, Pursel V G, Rexroad C E, et al. Production of transgenic rabbits, sheep and pigs by microinjection[J]. Nature,1985,315(6021): 680~683.
18 Houdebine L M. Transgenic animal bioreactors[J]. Transgenic Res,2000,9(4): 305~320.
19 Jaenisch R, Mintz R B. Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA[J]. Proc Natl Acad Sci,1974,71(4): 1250~1254.
20 Kang L, Wang J, Zhang Y, et al. iPS cells can support full-term development of tetraploid blastocyst-complemented embryos[J]. Cell Stem Cell,2009,5(2): 135~138.
21 Kim D, Kim C H, Moon J I, et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins[J]. Cell Stem Cell,2009a,4(6): 472.
22 Kim J B, Sebastiano V, Wu G, et al. Oct4-induced pluripotency in adult neural stem cells[J]. Cell,2009b,136(3): 411~419.
23 Klymiuk N, van Buerck L, Bahr A, et al. Xenografted islet cell clusters from INSLEA29Y ttransgenic pigs rescue diabetes and prevent immune rejection in humanized mice[J]. Diabetes,2012,61(6): 1527~1532.
24 Kunath T, Gish G, Lickert H, et al. Transgenic RNA interference in ES cell-derived embryos recapitulates a genetic null phenotype[J]. Nat Biotechnol,2003,21(5): 559~561.
25 Lai L, Kolber-Simonds D, Park K W, et al. Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning[J]. Science,2002,295(5557): 1089~1092.
26 Liu S, Li X, Lu D, et al. High-level expression of bioactive recombinant human lysozyme in the milk of transgenic mice using a modified human lactoferrin BAC[J]. Transgenic Res,2011,21(2): 407~414.
27 Maehr R, Chen S, Snitow M, et al. Generation of pluripotent stem cells from patients with type 1 diabetes[J]. Proc Natl Acad Sci,2009,106(37): 15768~15773.
28 Mayhall E A, Paffett-Lugassy N, Zon L I. The clinical potential of stem cells[J]. Curr Opin Cell Biol,2004,16(6): 713~720.
29 Miller J C, Holmes M C, Wang J, et al. An improved zinc-finger nuclease architecture for highly specific genome editing[J]. Nat Biotechnol,2007,25(7): 778~785.
30 Montserrat N, de Oñate L, Garreta E, et al. Generation of feeder free pig induced pluripotent stem cells without Pou5f1[J]. Cell Transplant,2012,21(5):815~825.
31 Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts[J]. Nat Biotechnol,2008,26(1): 101~106.
32 Onishi A, Iwamoto M, Akita T, et al. Pig cloning by microinjection of fetal fibroblast nuclei[J]. Science,2000,289(5482): 1188~1190.
33 Palmiter R, Brinster R, Hammer R. Dramatic growth of mice that develop metallothionein-growth hormone fusion genes[J]. Nature,1982,300(16): 611~615.
34 Park I H, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells[J]. Cell,2008,134(5): 877~886.
35 Piedrahita J A, Moore K, Oetama B, et al. Generation of transgenic porcine chimeras using primordial germ cell-derived colonies[J]. Biol Reprod,1998,58(5): 1321~1329.
36 Polejaeva I A, Chen S H, Vaught T D, et al. Cloned pigs produced by nuclear transfer from adult somatic cells[J]. Nature,2000,407(6800): 86~90.
37 Prelle K, Zink N, Wolf E. Pluripotent stem cells——model of embryonic development, tool for gene targeting, and basis of cell therapy[J]. Anat Histol Embryol,2002,31(3): 169~186.
38 Saeki K, Matsumoto K, Kinoshita M, et al. Functional expression of a Δ12 fatty acid desaturase gene from spinach in transgenic pigs[J]. Proc Natl Acad Sci,2004,101(17): 6361.
39 Sasaki E, Suemizu H, Shimada A, et al. Generation of transgenic non-human primates with germline transmission[J]. Nature,2009,459(7246): 523~527.
40 Schook L, Beattie C, Beever J, et al. Swine in biomedical research: Creating the building blocks of animal models[J]. Anim Biotechnol,2005,16(2): 183~190.
41 Shim H, Gutierrez-Adan A, Chen L R, et al. Isolation of pluripotent stem cells from cultured porcine primordial germ cells[J]. Biol Reprod,1997,57(5): 1089~1095.
42 Stadtfeld M, Hochedlinger K. Induced pluripotency: History, mechanisms, and applications[J]. Gene Dev,2010,24(20): 2239~2263.
43 Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors[J]. Cell,2007,131(5): 861~872.
44 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell,2006,126(4): 663~676.
45 Thomas K R, Capecchi M R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells[J]. Cell,1987,51(3): 503~512.
46 Thompson S, Clarke A R, Pow A M, et al. Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells[J]. Cell,1989,56(2): 313~321.
47 Thomson J A, Itskovitz-Eldor J, Shapiro S S, et al. Embryonic stem cell lines derived from human blastocysts[J]. Science,1998,282(5391): 1145~1147.
48 Thomson J A, Kalishman J, Golos T G, et al. Isolation of a primate embryonic stem cell line[J]. Proc Natl Acad Sci,1995,92(17): 7844.
49 Tong J, Wei H, Liu X, et al. Production of recombinant human lysozyme in the milk of transgenic pigs[J]. Transgenic Res,2011,20(2): 417~419.
50 Urnov F D, Miller J C, Lee Y L, et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases[J]. Nature,2005,435(7042): 646~651.
51 Wakayama T, Rodriguez I, Perry A C F, et al. Mice cloned from embryonic stem cells[J]. Proc Natl Acad Sci,1999,96(26): 14984.
52 Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state[J]. Nature,2007,448(7151): 318~324.
53 West F D, Terlouw S L, Kwon D J, et al. Porcine induced pluripotent stem cells produce chimeric offspring[J]. Stem Cells Dev,2010,19(8): 1211~1220.
54 West F D, Uhl E W, Liu Y, et al. Brief report: Chimeric pigs produced from induced pluripotent stem cells demonstrate germline transmission and no evidence of tumor formation in young pigs[J]. Stem Cells,2011,29(10): 1640~1643.
55 Wilmut I, Schnieke A E, McWhir J, et al. Viable offspring derived from fetal and adult mammalian cells[J]. Nature,1997,385(6619): 810~813.
56 Wu Z, Chen J, Ren J, et al. Generation of pig induced pluripotent stem cells with a drug-inducible system[J]. J Mol Cell Biol,2009,1(1): 46~54.
57 Yang D, Yang H, Li W, et al. Generation of PPARgamma mono-allelic knockout pigs via zinc-finger nucleases and nuclear transfer cloning[J]. Cell Res,2011,21(6): 979~982.
58 Yu J, Hu K, Smuga-Otto K, et al. Human induced pluripotent stem cells free of vector and transgene sequences[J]. Science,2009,324(5928): 797~801.
59 Yu J, Vodyanik M A, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells[J]. Science,2007,318(5858): 1917~1920.
60 Zhao X, Li W, Lv Z, et al. iPS cells produce viable mice through tetraploid complementation[J]. Nature,2009,461(7260): 86~90.
61 Zhao Y, Yin X, Qin H, et al. Two supporting factors greatly improve the efficiency of human iPSC generation[J]. Cell Stem Cell,2008,3(5): 475~479.
62 Zhou H, Wu S, Joo J Y, et al. Generation of induced pluripotent stem cells using recombinant proteins[J]. Cell Stem Cell,2010,4(5): 381~384.
63 Zou J, Maeder M L, Mali P, et al. Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells[J]. Cell Stem Cell,2009,5(1): 97~110.
64 Zwaka T P, Thomson J A. Homologous recombination in human embryonic stem cells[J]. Nat Biotechnol,2003,21(3): 319~321.

[1]	陈楷文, 赵云娇, 王磊, 张剑搏, 马玉红, 吴国芳. 不同氧浓度下猪睾丸间质细胞转录组分析[J]. 中国畜牧兽医, 2023, 50(6): 2185-2195.
[2]	韦明邦, 边巴琼达, 肖青青, 段梦琪, 强巴央宗, 商鹏. 藏猪CDKN1B基因克隆、生物信息学及表达分析[J]. 中国畜牧兽医, 2023, 50(6): 2196-2206.
[3]	张方玮, 张琪, 雷亮亮, 孙武胜, 张迪, 张云鹏, 张净搏, 王修权, 张晶, 张树敏. 松辽黑猪HBEGF基因多态性及其与繁殖性状的关联分析[J]. 中国畜牧兽医, 2023, 50(6): 2370-2379.
[4]	孙守湖, 陈志飞, 郭智轩, 俞婷, 王修武, 李松倍, 魏文康, 贺东生. 3种猪冠状病毒N基因密码子偏好性及宿主适应机制研究[J]. 中国畜牧兽医, 2023, 50(6): 2403-2413.
[5]	曹琪, 金清, 袁意, 冯逸雪, 孔丹妮, 陈翔鸿, 吴斌, 宋文博, 汤细彪. 规模化猪场常见呼吸道细菌性病原的流行病学调查[J]. 中国畜牧兽医, 2023, 50(6): 2439-2449.
[6]	史秋颖, 段宝敏, 李颖, 牛登云, 耿晨阳, 周佳伟, 王蕊, 冯敬敬. 2020—2021年中国部分地区猪流行性腹泻病毒S1基因遗传变异分析[J]. 中国畜牧兽医, 2023, 50(6): 2468-2478.
[7]	欧云文, 潘琴, 汪洋, 代军飞, 任绍科, 张洋, 张杰. 猪细小病毒6型ORF2基因的截短表达及多克隆抗体制备[J]. 中国畜牧兽医, 2023, 50(6): 2487-2495.
[8]	潘鹏丞, 雷宗全, 李显, 胡湘云, 秦谦涛, 覃兆鲜, 关志惠, 陈宝剑, 谢炳坤. 陆川猪MYL2基因生物信息学分析、真核表达载体构建及组织表达研究[J]. 中国畜牧兽医, 2023, 50(5): 1796-1806.
[9]	欧阳坤, 魏立民, 孙瑞萍, 解娅立, 齐琪, 李想, 刘圈炜, 晁哲, 张永亮, 陈婷. 姜黄素对海南屯昌猪生长性能、饲料养分表观消化率和血清生化指标的影响[J]. 中国畜牧兽医, 2023, 50(5): 1867-1875.
[10]	吴静璇, 孙征, 马雪莲, 张丽阳, 廖秀冬, 罗绪刚, 李素芬, 吕林. 中国畜禽饲料资源中镁含量的调查研究[J]. 中国畜牧兽医, 2023, 50(5): 1888-1898.
[11]	黎明国, 李清春, 陈鑫, 卢世豪, 何凡, 祁梦凡, 张化鹏, 任玉军, 张庆泽, 符彬彬, 徐梦思, 艾子凯, 闫坤, 冯赟, 华再东, 黄涛, 毕延震. TET去甲基化酶对猪卵母细胞发育的影响[J]. 中国畜牧兽医, 2023, 50(5): 1907-1917.
[12]	王泽平, 王飞飞, 张芮铭, 付言峰, 赵为民, 戴超辉, 程金花, 廖超, 李辉. 苏紫猪SLA-1基因多态性及其抗病潜能分析[J]. 中国畜牧兽医, 2023, 50(5): 1918-1927.
[13]	宋承磊, 张哲, 韦怡林, 杨松柏, 豆雅晴, 李晨雷, 刘蓥珂, 李新建, 杨峰, 李秀领, 王克君, 乔瑞敏, 韩雪蕾. 不同品种、季节和月龄对公猪精液品质的影响[J]. 中国畜牧兽医, 2023, 50(5): 1938-1946.
[14]	卓娜, 朱忠武, 李静, 胡世享, 王建昌, 林华, 陈朝林, 韩佃刚, 艾军, 陈培富. 猪源戊型肝炎病毒ORF2蛋白生物信息学分析及真核表达研究[J]. 中国畜牧兽医, 2023, 50(5): 1959-1970.
[15]	康溥, 任照文, 蔡汝健, 吕宗吉, 黄育浩, 王晓虎. 广东及周边省份猪繁殖与呼吸综合征病毒2型谱系8毒株变异规律和传播研究[J]. 中国畜牧兽医, 2023, 50(5): 2001-2011.