Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells
Chung, Young Gie
Eum, Jin Hee
Lee, Jeoung Eun
Cha, Kwang Yul
Lee, Dong Ryul
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CitationChung, Young Gie, Shogo Matoba, Yuting Liu, Jin Hee Eum, Falong Lu, Wei Jiang, Jeoung Eun Lee, et al. 2015. “Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells.” Cell Stem Cell (October). doi:10.1016/j.stem.2015.10.001.
AbstractThe 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:23520602
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