Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells
| Autor: | Kwang Yul Cha, Shogo Matoba, Vicken Sepilian, Young Gie Chung, Falong Lu, Yi Zhang, Wei Jiang, Jin Hee Eum, Yuting Liu, Jeoung Eun Lee, Dong Ryul Lee |
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| Rok vydání: | 2015 |
| Předmět: |
Pluripotent Stem Cells
Jumonji Domain-Containing Histone Demethylases Nuclear Transfer Techniques Transcription Genetic Somatic cell Biology somatic cell nuclear transfer Gene Expression Regulation Enzymologic H3K9me3 Histones Histone H3 Macular Degeneration Mice Heterochromatin medicine KDM4A Genetics Animals Humans Blastocyst human RNA Messenger Induced pluripotent stem cell ESC derivation Cell Nucleus Histone Demethylases Cumulus Cells reprogramming barrier Lysine Cell Biology Cellular Reprogramming Embryonic stem cell Cell biology medicine.anatomical_structure embryonic structures biology.protein Oocytes Demethylase Somatic cell nuclear transfer Molecular Medicine Female Reprogramming |
| Zdroj: | Cell stem cell. 17(6) |
| ISSN: | 1875-9777 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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