title: Ascorbic acid improves pluripotency of human parthenogenetic embryonic stem cells through modifying imprinted gene expression in the Dlk1-Dio3 region.
abstract: BACKGROUND
  Human parthenogenetic embryonic stem cells (hpESCs) are generated from artificially activated oocytes, however, the issue of whether hpESCs have equivalent differentiation ability to human fertilized embryonic stem cells remains controversial.
  
  
  METHODS
  hpESCs were injected into male severe combined immunodeficiency (SCID) mice and the efficiency of teratoma formation was calculated. Then the gene expression and methylation modification were detected by real time-PCR and bisulfate methods.
  
  
  RESULTS
  Comparison of five hpESCs with different differentiation abilities revealed that levels of paternal genes in the Dlk1-Dio3 region on chromosome 14 in the hpESCs with high differentiation potential are enhanced, but strictly methylated and silenced in the hpESCs with lower differentiation potential. Treatment with ascorbic acid, rescued their ability to support teratoma formation and altered the expression profiles of paternally expressed genes in hpESCs that could not form teratoma easily. No differences in the expression of other imprinting genes were evident between hpESCs with higher and lower differentiation potential, except for those in the Dlk1-Dio3 region.
  
  
  CONCLUSIONS
  The Dlk1-Dio3 imprinting gene cluster distinguishes the differentiation ability of hpESCs. Moreover, modification by ascorbic acid may facilitate application of hpESCs to clinical settings in the future by enhancing their pluripotency.
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. yuyang5012@hotmail.com.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China. yuyang5012@hotmail.com.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. yuyang5012@hotmail.com.
authors: Yang
authors: Y
authors: Yu
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. gaoqianbysy@126.com.
authors: Qian
authors: Q
authors: Gao
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. rainbowandsun@163.com.
authors: Hong-cui
authors: HC
authors: Zhao
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. roseli001@sina.com.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China. roseli001@sina.com.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. roseli001@sina.com.
authors: Rong
authors: R
authors: Li
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. jiangman1018@126.com.
authors: Jiang-man
authors: JM
authors: Gao
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. dingting0226@hotmail.com.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. dingting0226@hotmail.com.
authors: Ting
authors: T
authors: Ding
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. 75202485@qq.com.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China. 75202485@qq.com.
authors: Si-yu
authors: SY
authors: Bao
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. zhaoyue0630@163.com.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. zhaoyue0630@163.com.
authors: Yue
authors: Y
authors: Zhao
authors: Key Laboratory for Major Obstetric Diseases of Guangdong Province, the Third Affiliated Hospital of Guangzhou Medical University, No. 63, Liwan District, Guangzhou City, 510150, Guangdong Province, People's Republic of China. xiaofangsun@hotmail.com.
authors: Xiao-fang
authors: XF
authors: Sun
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. fanyong0413@sina.com.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, the Third Affiliated Hospital of Guangzhou Medical University, No. 63, Liwan District, Guangzhou City, 510150, Guangdong Province, People's Republic of China. fanyong0413@sina.com.
authors: Yong
authors: Y
authors: Fan
authors: Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Peking University Third Hospital, No. 49 HuaYuan North Road, HaiDian District, Beijing, 100191, People's Republic of China. jie.qiao@263.net.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China. jie.qiao@263.net.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. jie.qiao@263.net.
authors: Jie
authors: J
authors: Qiao
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D019175:DNA Methylation / Q000235:genetics; D046149:Embryo Culture Techniques; D053595:Embryonic Stem Cells / Q000187:drug effects*; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D007453:Iodide Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D005810:Multigene Family / Q000235:genetics; D010312:Parthenogenesis; D039904:Pluripotent Stem Cells / Q000187:drug effects; D013724:Teratoma / Q000235:genetics / Q000517:prevention & control*
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D001205:Ascorbic Acid