哺乳动物体细胞核移植表观遗传重编程研究进展

doi:10.16288/j.yczz.19-193

遗传 ›› 2019, Vol. 41 ›› Issue (12): 1099-1109.doi: 10.16288/j.yczz.19-193

哺乳动物体细胞核移植表观遗传重编程研究进展

杨旭琼, 吴珍芳, 李紫聪()

华南农业大学动物科学学院,国家生猪种业工程技术研究中心,广州 510642

收稿日期:2019-07-03 修回日期:2019-10-07 出版日期:2019-12-20 发布日期:2019-11-18
通讯作者: 李紫聪 E-mail:lizicongcong@163.com
作者简介:杨旭琼,硕士研究生,专业方向：动物遗传育种与繁殖。E-mail: 1814639793@qq.com
基金资助:
国家自然科学基金面上项目资助编号(31772554)

Advances in epigenetic reprogramming of somatic cells nuclear transfer in mammals

Xuqiong Yang, Zhenfang Wu, Zicong Li()

National Engineering Research Center for Swine Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China

Received:2019-07-03 Revised:2019-10-07 Online:2019-12-20 Published:2019-11-18
Contact: Li Zicong E-mail:lizicongcong@163.com
Supported by:
Supported by the National Natural Science Foundation of China No(31772554)

摘要/Abstract

摘要：

体细胞核移植(somatic cell nuclear transfer, SCNT)是唯一能赋予体细胞基因组全能性的生殖工程技术,对动物种质资源保存、畜牧业发展和生物医学研究等具有重大意义。尽管该技术已经取得了许多研究进展,但哺乳动物克隆胚胎的发育效率依然很低,严重限制其在畜牧业和生物医学上的应用。导致克隆胚胎发育效率低的主要原因是体细胞重编程错误或重编程不完全,主要表现为：印记基因Xist表达异常、DNA甲基化异常,组蛋白修饰异常等。本文简要介绍了体细胞核移植技术,系统总结了哺乳动物克隆胚胎发育效率低的主要影响因素,以期为提升体细胞克隆效率相关研究与实践提供理论参考。

关键词: 体细胞核移植, Xist, DNA甲基化, 组蛋白修饰

Abstract:

Somatic cell nuclear transfer (SCNT) is the only reproductive engineering technique that can confer genomic totipotency on somatic cell. SCNT is of great significance for animal germplasm conservation, animal husbandry development, and biomedical research. Although many research advances have been made in this technology, the developmental rate of SCNT mammalian embryos is very low, which seriously limits the application of SCNT in animal husbandry and biomedicine. The primary reason for the low efficiency of cloned embryos is somatic cell reprogramming errors or incomplete reprogramming. These errors or incompleteness present as the abnormal expression of imprinted gene Xist, abnormal DNA methylation, and abnormal histone modification. In this review, we summarize the main factors that influence the low development efficiency of mammalian cloned embryos to provide theoretical reference for the research and practice of improving somatic cell cloning efficiency.

Key words: somatic cell nuclear transfer (SCNT), Xist, DNA methylation, histone modification

杨旭琼, 吴珍芳, 李紫聪. 哺乳动物体细胞核移植表观遗传重编程研究进展[J]. 遗传, 2019, 41(12): 1099-1109.

Xuqiong Yang, Zhenfang Wu, Zicong Li. Advances in epigenetic reprogramming of somatic cells nuclear transfer in mammals[J]. Hereditas(Beijing), 2019, 41(12): 1099-1109.

图/表 2

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SCNT胚胎发育效率^{[44,45,47,50,94]}		影响SCNT胚胎发育效率的表观遗传重编程因素	对策	结果
体外(囊胚率)	体内(出生率)	影响SCNT胚胎发育效率的表观遗传重编程因素	对策	结果
15% ~	1%~5%	Xist	KO-Xist;注射siRNA	克隆小鼠出生率提高8~9倍^[8]; 克隆小鼠囊胚率以及出生率提高10倍^[9];克隆猪出生率提高6.9倍^[64]
		DNA甲基化	抑制DNMT	克隆小鼠出生率提高5倍^[75]
		组蛋白乙酰化水平	添加HDACi药物	克隆猪囊胚率提高2倍^[81]; 克隆小鼠囊胚率提高5~10倍^[80]
		H3K9me3	注射Kdm4d或联合KO-Xist; 联合注射Kdm4b和Kdm5b	克隆小鼠出生率提高13~16倍^[74]; 克隆小鼠囊胚率达95%^[10]
		H3K27me3	注射Kdm6a	克隆小鼠囊胚率提高2倍^[95]

哺乳动物体细胞核移植表观遗传重编程研究进展

Advances in epigenetic reprogramming of somatic cells nuclear transfer in mammals

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