title: Telomere elongation and naive pluripotent stem cells achieved from telomerase haplo-insufficient cells by somatic cell nuclear transfer.
abstract: Haplo-insufficiency of telomerase genes in humans leads to telomere syndromes such as dyskeratosis congenital and idiopathic pulmonary fibrosis. Generation of pluripotent stem cells from telomerase haplo-insufficient donor cells would provide unique opportunities toward the realization of patient-specific stem cell therapies. Recently, pluripotent human embryonic stem cells (ntESCs) have been efficiently achieved by somatic cell nuclear transfer (SCNT). We tested the hypothesis that SCNT could effectively elongate shortening telomeres of telomerase haplo-insufficient cells in the ntESCs with relevant mouse models. Indeed, telomeres of telomerase haplo-insufficient (Terc(+/-)) mouse cells are elongated in ntESCs. Moreover, ntESCs derived from Terc(+/-) cells exhibit naive pluripotency as evidenced by generation of Terc(+/-) ntESC clone pups by tetraploid embryo complementation, the most stringent test of naive pluripotency. These data suggest that SCNT could offer a powerful tool to reprogram telomeres and to discover the factors for robust restoration of telomeres and pluripotency of telomerase haplo-insufficient somatic cells.
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 115 Taiwan, ROC; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 100 Taiwan, ROC.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Sung
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC.
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC; Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350 Taiwan, ROC.
authors.forename: Chia-Chia
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350 Taiwan, ROC.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Liou
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC.
authors.forename: Huan
authors.initials: H
authors.lastname: Ou-Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Renpeng
authors.initials: R
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Fu
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC; Department of Animal Science and Biotechnology, Tunghai University, Taichung, 407 Taiwan, ROC.
authors.forename: Winston T K
authors.initials: WTK
authors.lastname: Cheng
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC.
authors.forename: Shih-Torng
authors.initials: ST
authors.lastname: Ding
authors.affiliation: Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung, 402 Taiwan, ROC; Rong-Hsing Translational Medicine Center and iEGG Center, National Chung Hsing University, Taichung, 402 Taiwan, ROC.
authors.forename: Chuan-Mu
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33612, USA.
authors.forename: Maja
authors.initials: M
authors.lastname: Okuka
authors.affiliation: Department of Obstetrics and Gynecology, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Keefe
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: liulin@nankai.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address: jiex@umich.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D057895:Haploinsufficiency; D057026:Induced Pluripotent Stem Cells / Q000201:enzymology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053652:Nuclear Transfer Techniques; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis
chemical_list: D019098:Telomerase