体细胞核移植后表观遗传重编程的异常及其修复

doi:10.3724/SP.J.1005.2014.1211

遗传 ›› 2014, Vol. 36 ›› Issue (12): 1211-1218.doi: 10.3724/SP.J.1005.2014.1211

体细胞核移植后表观遗传重编程的异常及其修复

纪慧丽^{1, 2}, 卢晟盛¹, 潘登科²

1. 广西大学动物科学技术学院, 亚热带农业生物资源保护与利用国家重点实验室, 南宁 530004;
2. 中国农业科学院北京畜牧兽医研究所, 农业部畜禽遗传资源与种质创新重点实验室, 北京 100193

收稿日期:2014-07-17 出版日期:2014-12-20 发布日期:2014-12-20
通讯作者: 潘登科, 博士, 副研究员, 研究方向：动物胚胎生物技术。E-mail: pandengke2002@163.com卢晟盛, 博士, 研究员, 博士生导师, 研究方向：动物繁殖生物技术。E-mail: sslu@gxu.edu.cn E-mail:jihuili1989@163.com
作者简介:纪慧丽, 硕士研究生, 专业方向：动物胚胎生物技术。
基金资助:
转基因生物新品种培育重大专项(编号：2014ZX0800605B)和国家高技术研究发展计划(863计划)项目(编号：2012AA020601)资助

Epigenetic reprogramming by somatic cell nuclear transfer: questions and potential solutions

Ji Huili^{1, 2}, Lu Shengsheng¹, Pan Dengke²

1. State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, China;
2. Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Received:2014-07-17 Online:2014-12-20 Published:2014-12-20

摘要/Abstract

摘要：

体细胞核移植(Somatic cell nuclear transfer, SCNT)是指将高度分化的体细胞移入到去核的卵母细胞中发育并最终产生后代的技术。然而, 体细胞克隆的总体效率仍然处于一个较低的水平, 主要原因之一是由于体细胞供体核不完全的表观遗传重编程, 包括DNA甲基化、组蛋白乙酰化、基因组印记、X染色体失活和端粒长度等修饰出现的异常。使用一些小分子化合物以及Xist基因的敲除或敲低等方法能修复表观遗传修饰错误, 辅助供体核的重编程, 从而提高体细胞克隆效率, 使其更好地应用于基础研究和生产实践。文章对体细胞核移植后胚胎发育过程中出现的异常表观遗传修饰进行了综述, 并着重论述了近年来有关修复表观遗传错误的研究进展。

关键词: 体细胞核移植, 重编程, 表观遗传异常, 小分子化合物

Abstract:

Somatic cell nuclear transfer (SCNT) is a technology by which a highly differentiated somatic nucleus is transferred into an enucleated oocyte to generate a reconstructed embryo that subsequently develops to an offspring. However, to date, the efficiency of cloned animal is still low. The major reason is incomplete nuclear reprogramming of donor cells after nuclear transfer, which results in abnormal epigenetic modifications, including DNA methylation, histone acetylation, gene imprinting, X-chromosome inactivation, and telomere length. Most improvements have been made in somatic epigenetic reprogramming with small molecules and manipulating expression of specific genes. It is expected that SCNT will soon have broad applications in both basic research and practical production. In this review, we summarize the recent progress in epigenetic reprogramming by somatic cell nuclear transfer; in particular, we focus on strategies for rescuing the epigenetic errors occurring during SCNT.

Key words: SCNT, reprogramming, epigenetic errors, small molecules

纪慧丽, 卢晟盛, 潘登科. 体细胞核移植后表观遗传重编程的异常及其修复[J]. 遗传, 2014, 36(12): 1211-1218.

Ji Huili, Lu Shengsheng, Pan Dengke. Epigenetic reprogramming by somatic cell nuclear transfer: questions and potential solutions[J]. HEREDITAS(Beijing), 2014, 36(12): 1211-1218.

参考文献

[1] Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KHS. Viable offspring derived from fetal and adult mam-malian cells. Nature, 1997, 385(6619): 810–813.
[2] Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de León FA, Robl JM. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science, 1998, 280(5367): 1256–1258.
[3] Wakayama T, Perry ACF, Zuccotti M, Johnson KR, Yan-agimachi R. Full-term development of mice from enucle-ated oocytes injected with cumulus cell nuclei. Nature, 1998, 394(6691): 369–374.
[4] Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry ACF. Pig cloning by microinjection of fetal fibroblast nuclei. Science, 2000, 289(5482): 1188–1190.
[5] Shin T, Kraemer D, Pryor J, Liu L, Rugila J, Howe L, Buck S, Murphy K, Lyons L, Westhusin M. A cat cloned by nuclear transplantation. Nature, 2002, 415(6874): 589.
[6] Chesné P, Adenot PG, Viglietta C, Baratte M, Boulanger L, Renard JP. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nat Biotechnol, 2002, 20(4): 366–369.
[7] Young LE, Sinclair KD, Wilmut I. Large offspring syndrome in cattle and sheep. Rev Reprod, 1998, 3(3): 155–163.
[8] Ono Y, Shimozawa N, Ito M, Kono T. Cloned mice from fetal fibroblast cells arrested at metaphase by a serial nu-clear transfer. Biol Reprod, 2001, 64(1): 44–50.
[9] Chavatte-Palmer P, Heyman Y, Richard C, Monget P, LeBourhis D, Kann G, Chilliard Y, Vigon X, Renard JP. Clinical, hormonal, and hematologic characteristics of bo-vine calves derived from nuclei from somatic cells. Biol Reprod, 2002, 66(6): 1596–1603.
[10] Eggan K, Akutsu H, Loring J, Jackson-Grusby L, Klemm M, Rideout WM 3rd, Yanagimachi R, Jaenisch R. Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation. Proc Natl Acad Sci USA, 2001, 98(11): 6209–6214.
[11] Kang YK, Koo DB, Park JS, Choi YH, Chung AS, Lee KK, Han YM. Aberrant methylation of donor genome in clo-ned bovine embryos. Nat Genet, 2001, 28(2): 173–177.
[12] Jeanisch R, Eggan K, Humpherys D, Rideout W, Hochedlinger K. Nuclear cloning, stem cells, and genomic reprogramming. Cloning Stem Cells, 2002, 4(4): 389–396.
[13] Costa-Borges N, Gonzalez S, Santaló J, Ibá?ez E. Effect of the enucleation procedure on the reprogramming potential and developmental capacity of mouse cloned embryos treated with valproic acid. Reproduction, 2011, 141(6): 789– 800.
[14] Wakayama S, Cibelli JB, Wakayama T. Effect of timing of the removal of oocyte chromosomes before or after injec-tion of somatic nucleus on development of NT embryos. Cloning Stem Cells, 2003, 5(3): 181–189.
[15] Enright B, Kubota C, Yang X, Tian XC. Epigenetic char-acteristics and development of embryos cloned from do-nor cells treated by trichostatin A or 5-aza-2'-deoxycy?tidine. Biol Reprod, 2003, 69(3): 896–901.
[16] Kurome M, Hisatomi H, Matsumoto S, Tomii R, Ueno S, Hiruma K, Saito H, Nakamura K, Okumura K, Matsumoto M, Kaji Y, Endo F, Nagashima H. Production efficiency and telomere length of the cloned pigs following serial somatic cell nuclear transfer. J Reprod Dev, 2008, 54(4): 254–258.
[17] Kang YK, Park J, Koo DB, Choi YH, Kim SU, Lee KK, Han YM. Limited demethylation leaves mosaic-type methylation states in cloned bovine pre-implantation em-bryos. EMBO J, 2002, 21(5): 1092–1100.
[18] Dean W, Santoa F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W. Conservation of methylation repro-gramming in mammalian development: aberrant repro-gramming in cloned embryos. Proc Natl Acad Sci USA, 2001, 98(24): 13734–13738.
[19] Beaujean N, Taylor J, Garden J, Wilmut I, Meehan R, Young L. Effect of limited DNA methylation reprogramming in the normal sheep embryo on somatic cell nuclear transfer. Biol Reprod, 2004, 71(1): 185–193.
[20] Garcia BA, Hake SB, Diaz RL, Kauer M, Morris SA, Recht J, Shabanowitz J, Mishra N, Strahl BD, Allis CD, Hunt DF. Organismal differences in post-translational modifications in histones H3 and H4. J Biol Chem, 2007, 282(10): 7641–7655.
[21] Enright BP, Sung LY, Chang CC, Yang X, Tian XC. Meth-ylation and acetylation characteristics of cloned bovine embryos from donor cells treated with 5-aza-2'-deoxycy-tidine. Biol Reprod, 2005, 72(4): 944–948.
[22] Suteevun T, Parnpai R, Smith SL, Chang CC, Muenthaisong S, Tian XC. Epigenetic characteristics of cloned and in vitro-fertilized swamp buffalo (Bubalus bubalis) embryos. J Anim Sci, 2006, 84(8): 2065–2071.
[23] Bui HT, Van Thuan N, Wakayama T, Miyano T. Chromatin remodeling in somatic cells injected into mature pig oo-cytes. Reproduction, 2006, 131(6): 1037–1049.
[24] Wang FC, Kou ZH, Zhang Y, Gao SR. Dynamic repro-gramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos. Biol Reprod, 2007, 77(6): 1007–1016.
[25] Papp B, Müller J. Histone trimethylation and the mainte-nance of transcriptional ON and OFF states by trxG and PcG protein. Genes Dev, 2006, 20(15): 2041–2054.
[26] Zhang M, Wang FC, Kou ZH, Zhang Y, Gao SR. Defec-tive chromatin structure in somatic cell cloned mouse em-bryos. J Biol Chem, 2009, 284(37): 24981–24987.
[27] Kalantry S, Purushothaman S, Bowen RB, Starmer J, Magnuson T. Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation. Nature, 2009, 460(7255): 647–651.
[28] Nolen LD, Gao SR, Han ZM, Mann MRW, Chung YG, Otte AP, Bartolomei MS, Latham KE. X chromosome re-activation and regulation in cloned embryos. Dev Biol, 2005, 279(2): 525–540.
[29] Inoue K, Kohda T, Sugimoto M, Sado T, Ogonuki N, Matoba S, Shiura H, Ikeda R, Mochida K, Fujii T, Sawai K, Otte AP, Tian XC, Yang XZ, Ishino F, Abe K, Ogura A. Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer. Science, 2010, 330(6003): 496–499.
[30] Xue F, Tian XC, Du FL, Kubota C, Taneja M, Dinnyes A, Dai YP, Levine H, Pereira LV, Yang XZ. Aberrant patterns of X chromosome inactivation in bovine clones. Nat Genet, 2002, 31(2): 216–220.
[31] Smith SL, Everts RE, Tian XC, Du FL, Sung LY, Rodri-guez-Zas SL, Jeong BS, Renard JP, Lewin HA, Yang XZ. Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning. Proc Natl Acad Sci USA, 2005, 102(49): 17582–17587.
[32] Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout WM 3rd, Biniszkiewicz D, Yanagimachi R, Jaenisch R. Epigenetic instability in ES cells and cloned mice. Science, 2001, 293(5527): 95–97.
[33] Constancia M, Pickard B, Kelsey G, Reik W. Imprinting mechanisms. Genome Res, 1998, 8(9): 881–900.
[34] Han DW, Song SJ, Uhum SJ, Do JT, Kim NH, Chung KS, Lee HT. Expression of IGF2 and IGF receptor mRNA in bovine nuclear transferred embryos. Zygote, 2003, 11(3): 245–252.
[35] Inoue K, Kohda T, Lee J, Ogonuki N, Mochida K, Noguchi Y, Tanemura K, Kaneko-Ishino T, Ishino F, Ogura A. Faithful expression of imprinted genes in cloned mice. Science, 2002, 295(5553): 297.
[36] Yang L, Chavatte-Palmer P, Kubota C, O’Neill M, Hoagland T, Renard JP, Taneja M, Yang XZ, Tian XC. Expression of imprinted genes is aberrant in deceased newborn cloned calves and relatively normal in surviving adult clones. Mol Reprod Dev, 2005, 71(4): 431–438.
[37] Wei YC, Zhu J, Huan YJ, Liu ZF, Yang CR, Zhang XM, Mu YS, Xia P, Liu ZH. Aberrant expression and methylation status of putatively imprinted genes in placenta of cloned piglets. Cell Reprogram, 2010, 12(2): 213–222. [38] Blackburn EH. The telomere and telomerase: nucleic ac-id-protein complexes acting in a telomere homeostasis system. A review. Biochemistry, 1997, 62(11): 1196–1201.
[39] Shiels PG, Kind AJ, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE. Analysis of telomere lengths in cloned sheep. Nature, 1999, 399(6734): 316–317.
[40] Jeon HY, Hyun SH, Lee GS, Kim HS, Kim S, Jeong YW, Kang SK, Lee BC, Han JY, Ahn C, Hwang WS. The analysis of telomere length and telomerase activity in cloned pigs and cows. Mol Reprod Dev, 2005, 71(3): 315–320.
[41] Miyashita N, Shiga K, Yonai M, Kaneyama K, Kobayashi S, Kojima T, Goto Y, Kishi M, Aso H, Suzuki T, Sakaguchi M, Nagai T. Remarkable differences in telomere lengths among cloned cattle derived from different cell types. Biol Reprod, 2002, 66(6): 1649–1655.
[42] Niemann H, Tian XC, King WA, Lee RS. Epigenetic re-programming in embryonic and foetal development upon somatic cell nuclear transfer cloning. Reproduction, 2008, 135(2): 151–163.
[43] Jafari S, Hosseini MS, Hajian M, Forouzanfar M, Jafarpour F, Abedi P, Ostadhosseini S, Abbasi H, Gourabi H, Shahverdi AH, Dizaj AV, Anjomshoaa M, Haron W, Noorshariza N, Yakub H, Nasr-Esfahani MH. Improved in vitro development of cloned bovine Embryos using S-adenosylhomocysteine, a non-toxic epigenetic modifying reagent. Mol Reprod Dev, 2011, 78(8): 576–584.
[44] Wang YS, Xiong XR, An ZX, Wang LJ, Liu J, Quan FS, Hua S, Zhang Y. Production of cloned calves by combination treatment of both donor cells and early cloned embryos with 5-aza-2'-deoxycytidine and trichostatin A. Theriogenology, 2011, 75(5): 819–825.
[45] Xu WH, Li ZC, Yu B, He XY, Shi JS, Zhou R, Liu DW, Wu ZF. Effects of DNMT1 and HDAC inhibitors on gene-specific methylation reprogramming during porcine somatic cell nuclear transfer. PLoS ONE, 2013, 8(5): e64705.
[46] Ono T, Li C, Mizutani E, Terashita Y, Yamagata K, Waka-yama T. Inhibition of class IIb histone deacetylase signif-icantly improves cloning efficiency in mice. Biol Reprod, 2010, 83(6): 927–937.
[47] Akagi S, Matsukawa K, Mizutani E, Fukunari K, Kaneda M, Watanabe S, Takahashi S. Treatment with a histone deacetylase inhibitor after nuclear transfer improves the preimplantation development of cloned bovine embryos. J Reprod Dev, 2011, 57(1): 120–126.
[48] Lee MJ, Kim SW, Lee HG, Im GS, Yang BC, Kim NH, Kim DH. Trichostatin A promotes the development of bovine somatic cell nuclear transfer embryos. J Reprod Dev, 2011, 57(1): 34–42.
[49] Yamanaka K, Sugimura S, Wakai T, Kawahara M, Sato E. Acetylation level of histone H3 in early embryonic stages affects subsequent development of miniature pig somat-ic cell nuclear transfer embryos. J Reprod Dev, 2009, 55(6): 638–644.
[50] Meng QG, Polgar Z, Liu J, Dinnyes A. Live birth of so-matic cell-cloned rabbits following trichostatin A treatment and cotransfer of parthenogenetic embryos. Cloning Stem Cells, 2009, 11(1): 203–208.
[51] Kishigami S, Mizutani E, Ohta H, Hikichi T, Van Thuan N, Wakayama S, Bui HT, Wakayama T. Significant im-provement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochem Bi-ophys Res Commun, 2006, 340(1): 183–189.
[52] Wakayama T, Kohda T, Obokata H, Tokoro M, Li C, Terashita Y, Mizutani E, Nguyen VT, Kishigami S, Ishino F, Wakayama T. Successful Serial Recloning in the mouse over multiple generations. Cell Stem Cell, 2013, 12(3): 293–297.
[53] Wakayama S, Wakayama T. Improvement of mouse cloning using nuclear transfer-derived embryonic stem cells and/or histone deacetylase inhibitor. Int J Dev Biol, 2010, 54(11–12): 1641–1648.
[54] Van Thuan N, Bui HT, Kim JH, Hikichi T, Wakayama S, Kishigami S, Mizutani E, Wakayama T. The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescues full-term development in cloned inbred mice. Reproduction, 2009, 138(2): 309–317.
[55] Su JM, Wang YS, Li YY, Li RZ, Li Q, Wu YY, Quan FS, Liu J, Guo ZK, Zhang Y. Oxamflatin significantly improves nuclear reprogramming, blastocyst quality, and in vitro development of bovine SCNT embryos. PLoS ONE, 2011, 6(8): e23805.
[56] Miyoshi K, Mori H, Mizobe Y, Akasaka E, Ozawa A, Yo-shida M, Sato M. Valproic acid enhances in vitro devel-opment and Oct-3/4 expression of miniature pig somatic cell nuclear transfer embryos. Cell Reprogram, 2010, 12(1): 67–74.
[57] Xu W, Wang Y, Li Y, Wang L, Xiong X, Su J, Zhang Y. Valproic acid improves the in vitro development compe-tence of bovine somatic cell nuclear transfer embryos. Cell Reprogram, 2012, 14(2): 138–145.
[58] Kim YJ, Ahn KS, Kim M, Shim H. Comparison of poten-cy between histone deacetylase inhibitors trichostatin A and valproic acid on enhancing in vitro development of porcine somatic cell nuclear transfer embryos. In Vitro Cell Dev Biol Anim, 2011, 47(4): 283–289.
[59] Isaji Y, Murata M, Takaguchi N, Mukai T, Tajima Y, Imai H, Yamada M. Valproic acid treatment from the 4-cell stage improves Oct4 expression and nuclear distribution of histone H3K27me3 in mouse cloned blastocysts. J Reprod Dev, 2013, 59(2): 196–204.
[60] Jin JX, Li S, Gao QS, Hong Y, Jin L, Zhu HY, Yan CG, Kang JD, Yin XJ. Significant improvement of pig cloning efficiency by treatment with LBH589 after somatic cell nuclear transfer. Theriogenology, 2013, 80(6): 630–635.
[61] Jin JX, Li S, Hong Y, Jin L, Zhu HY, Guo Q, Gao QS, Yan CG, Kang JD, Yin XJ. CUDC-101, a histone deacetylase inhibitor, improves the in vitro and in vivo developmen-tal competence of somatic cell nuclear transfer pig embryos. Theriogenology, 2014, 81(4): 572–578.
[62] Song YR, Hai T, Wang Y, Guo R, Li W, Wang L, Zhou Q. Epigenetic reprogramming, gene expression and in vitro development of porcine SCNT embryos are significantly improved by a histone deacetylase inhibitor-m-carboxyci-nnamic acid bishydroxamide (CBHA). Protein Cell, 2014, 5(5): 382–393.
[63] Dai XP, Hao J, Hou XJ, Hai T, Fan Y, Yu Y, Jouneau A, Wang L, Zhou Q. Somatic nucleus reprogramming is significantly improved by m-carboxycinnamic acid bishydroxamide, a histone deacetylase inhibitor. J Biol Chem, 2010, 285(40): 31002–31010.
[64] Ogura A, Inoue K, Wakayama T. Recent advancements in cloning by somatic cell nuclear transfer. Phil Trans R Soc Lond B Biol Sci, 2013, 368(1609): 20110329.
[65] Matoba S, Inoue K, Kohda T, Sugimoto M, Mizutani E, Ogonuki N, Nakamura T, Abe K, Nakano T, Ishino F, Ogura A. RNAi-mediated knockdown of Xist can rescue the impaired postimplantation development of cloned mouse embryos. Proc Natl Acad Sci USA, 2011, 108(51): 20621–20626.
[66] Zhou W, Wang K, Ruan W, Bo Z, Liu L, Cao Z, Chai L, Cao G. Higher methylation in genomic DNA indicates in-complete reprogramming in induced pluripotent stem cells. Cell Reprogram, 2013, 15(1): 92–99.
[67] Ma H, Morey R, O'Neil RC, He Y, Daughtry B, Schultz MD, Hariharan M, Nery JR, Castanon R, Sabatini K, Thiagarajan RD, Tachibana M, Kang E, Castanon R, Sabatini K, Thiagarajan RD, Tachibana M, Kang E, Tippner-Hedges R, Ahmed R, Gutierrez NM, Van Dyken C, Polat A, Sugawara A, Sparman M, Gokhale S, Amato P, Wolf DP, Ecker JR, Laurent LC, Mitalipov S. Abnormalities in human pluripotent cells due to reprogramming mech?anisms. Nature, 2014, 511(7508): 177–183.
[68] Hikichi T, Ohta H, Wakayama S, Wakayama T. Functional full-term placentas formed from parthenogenetic embryos using serial nuclear transfer. Development, 2010, 137(17): 2841–2847.
[69] Okae H, Matoba S, Nagashima T, Mizutani E, Inoue K, Ogonuki N, Chiba H, Funayama R, Tanaka S, Yaegashi N, Nakayama K, Sasaki H, Ogura A, Arima T. RNA se-quencing-based identification of aberrant imprinting in cloned mice. Hum Mol Genet, 2014, 23(4): 992–1001.
[70] Matoba S, Liu YT, Lu FL, Iwabuchi KA, Shen L, Inoue A, Zhang Y. Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation. Cell, 2014, 159(4):1–12.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

体细胞核移植后表观遗传重编程的异常及其修复

Epigenetic reprogramming by somatic cell nuclear transfer: questions and potential solutions

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	张凤霞,王国栋. 现代代谢组学平台建设及相关技术应用[J]. 遗传, 2019, 41(9): 883-892.
[2]	黄星卫, 程香荣, 王楠, 张雨薇, 廖辰, 金连弘, 雷蕾. 组蛋白H3变体H3.3及其在细胞重编程中的作用[J]. 遗传, 2018, 40(3): 186-196.
[3]	康岚, 陈嘉瑜, 高绍荣. 中国细胞重编程和多能干细胞研究进展[J]. 遗传, 2018, 40(10): 825-840.
[4]	张玲, 何建波. GATA6在肝脏发育中的作用及调控机制[J]. 遗传, 2018, 40(1): 22-32.
[5]	贾振伟. 线粒体与多潜能干细胞功能[J]. 遗传, 2016, 38(7): 603-611.
[6]	敖政, 刘德武, 蔡更元, 吴珍芳, 李紫聪. 克隆哺乳动物的胎盘发育缺陷[J]. 遗传, 2016, 38(5): 402-410.
[7]	余莉莉,董琬如,陈明会,孔祥阳. 性腺母细胞瘤的分子遗传机制研究进展[J]. 遗传, 2015, 37(11): 1105-1115.
[8]	任才芳，孙红艳，王立中，张国敏，樊懿萱，颜光耀，王丹，王锋. iPSCs遗传稳定性与重编程机制的研究进展[J]. 遗传, 2014, 36(9): 879-887.
[9]	曹明君, 董焕生, 潘庆杰, 王红军, 董晓. 胰腺早期发育及终末分化细胞重编程为胰岛β细胞的研究进展[J]. 遗传, 2014, 36(6): 511-518.
[10]	宋红卫, 安铁洙, 朴善花, 王春生. 哺乳动物DNA甲基化及其在体细胞诱导重编程中的作用[J]. 遗传, 2014, 36(5): 431-438.
[11]	马克学, 马克世, 席兴字. 表观遗传跨代继承表型研究进展[J]. 遗传, 2014, 36(5): 476-484.
[12]	范宗兴，朱化彬，杜卫华. 细胞抽提物诱导的体细胞重编程[J]. 遗传, 2013, 35(3): 262-268.
[13]	孙红艳，王锋，曹文广. 细胞命运转变——谱系重编程技术研究进展[J]. 遗传, 2012, 34(8): 985-992.
[14]	陈倩，史庆华. iPS细胞的遗传安全性[J]. 遗传, 2012, 34(3): 260-268.
[15]	王春生，张志人，朴善花，安铁洙. microRNA在诱导体细胞重编程中的作用[J]. 遗传, 2012, 34(12): 1545-1550.