Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells

被引：163

作者：

Chung, Young Gie ^{[1
,2
]}

Matoba, Shogo ^{[3
,4
,5
]}

Liu, Yuting ^{[3
,4
,5
]}

Eum, Jin Hee ^{[2
]}

Lu, Falong ^{[3
,4
,5
]}

Jiang, Wei ^{[3
,4
,5
]}

Lee, Jeoung Eun ^{[2
]}

Sepilian, Vicken ^{[1
]}

Cha, Kwang Yul ^{[2
]}

Lee, Dong Ryul ^{[1
,2
]}

Zhang, Yi ^{[3
,4
,5
,6
]}

机构：

[1] CHA Hlth Syst, Res Inst Stem Cell Res, Los Angeles, CA 90036 USA

[2] CHA Univ, CHA Stem Cell Inst, Seoul 135081, South Korea

[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA

来源：

CELL STEM CELL | 2015年 / 17卷 / 06期

基金：

日本学术振兴会;

关键词：

IMPLANTATION; PREGNANCY; EMBRYOS; RATES;

D O I：

10.1016/j.stem.2015.10.001

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The extremely low efficiency of human embryonic stem cell (hESC) derivation using somatic cell nuclear transfer (SCNT) limits its potential application. Blastocyst formation from human SCNT embryos occurs at a low rate and with only some oocyte donors. We previously showed in mice that reduction of histone H3 lysine 9 trimethylation (H3K9me3) through ectopic expression of the H3K9me3 demethylase Kdm4d greatly improves SCNT embryo development. Here we show that overexpression of a related H3K9me3 demethylase KDM4A improves human SCNT, and that, as in mice, H3K9me3 in the human somatic cell genome is an SCNT reprogramming barrier. Overexpression of KDM4A significantly improves the blastocyst formation rate in human SCNT embryos by facilitating transcriptional reprogramming, allowing efficient derivation of SCNT-derived ESCs using adult Age-related Macular Degeneration (AMD) patient somatic nuclei donors. This conserved mechanistic insight has potential applications for improving SCNT in a variety of contexts, including regenerative medicine.

引用

页码：758 / 766

页数：9

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