title: Derivation of cloned human blastocysts by histone deacetylase inhibitor treatment after somatic cell nuclear transfer with β-thalassemia fibroblasts.
abstract: Derivation of embryonic stem cells from patient-specific cloned blastocysts by somatic cell nuclear transfer (SCNT) holds promise for both regenerative medicine and cell-based drug discovery. However, the efficiency of blastocyst formation after human SCNT is very low. The developmental competence of SCNT embryos has been previously demonstrated in several species to be enhanced by treatment with histone deacetylase inhibitors, such as trichostatin A (TSA), to increase histone acetylation. In this study, we report that treatment of SCNT embryos with 5  nM TSA for 10  h following activation incubation increased the developmental competence of human SCNT embryos constructed from β-thalassemia fibroblast cells. The efficiency of blastocyst formation from SCNT human embryos treated with TSA was approximately 2 times greater than that from untreated embryos. Cloned blastocysts were confirmed to be generated through SCNT by DNA and mitochondrial DNA fingerprinting analyses. Further, treatment of SCNT embryos with TSA improved the acetylation of histone H3 at lysine 9 in a manner similar to that observed in in vitro fertilized embryos.
authors.affiliation: Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xinjie
authors.initials: X
authors.lastname: Chen
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Ou
authors.forename: Yifei
authors.initials: Y
authors.lastname: Yin
authors.forename: Shengchang
authors.initials: S
authors.lastname: Huang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Kou
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Long
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Liu
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Luo
authors.forename: Baoping
authors.initials: B
authors.lastname: Liao
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sun
mesh_terms: D000107:Acetylation; D001483:Base Sequence; D001755:Blastocyst / Q000473:pathology; D001757:Blastomeres / Q000187:drug effects* / Q000378:metabolism; D048430:Cell Shape; D002478:Cells, Cultured; D019976:Cloning, Organism; D018920:Coculture Techniques; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D059785:Karyotype; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D053652:Nuclear Transfer Techniques; D017422:Sequence Analysis, DNA; D020554:Sperm Injections, Intracytoplasmic; D017086:beta-Thalassemia / Q000473:pathology*
chemical_list: D004272:DNA, Mitochondrial; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A