Telomere Elongation and Naive Pluripotent Stem Cells Achieved from Telomerase Haplo-Insufficient Cells by Somatic Cell Nuclear Transfer
Li-Ying Sung,
Wei-Fang Chang,
Qian Zhang,
Chia-Chia Liu,
Jun-Yang Liou,
Chia-Chun Chang,
Huan Ou-Yang,
Renpeng Guo,
Haifeng Fu,
Winston T.K. Cheng,
Shih-Torng Ding,
Chuan-Mu Chen,
Maja Okuka,
David L. Keefe,
Y. Eugene Chen,
Lin Liu,
Jie Xu
Affiliations
Li-Ying Sung
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
Wei-Fang Chang
Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC
Qian Zhang
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
Chia-Chia Liu
Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC; Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350 Taiwan, ROC
Jun-Yang Liou
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350 Taiwan, ROC
Chia-Chun Chang
Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC
Huan Ou-Yang
Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC
Renpeng Guo
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
Haifeng Fu
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
Winston T.K. Cheng
Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC; Department of Animal Science and Biotechnology, Tunghai University, Taichung, 407 Taiwan, ROC
Shih-Torng Ding
Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC
Chuan-Mu Chen
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
Maja Okuka
Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33612, USA
David L. Keefe
Department of Obstetrics and Gynecology, New York University Langone Medical Center, New York, NY 10016, USA
Y. Eugene Chen
Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Lin Liu
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; Corresponding author
Jie Xu
Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; Corresponding author
Summary: 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. : Sung et al. demonstrate in a mouse model that telomeres of telomerase haplo-insufficient cells can be elongated by somatic cell nuclear transfer. Moreover, ntESCs derived from Terc+/− cells exhibit pluripotency evidenced by generation of Terc+/−ntESC clone pups by tetraploid embryo complementation, the most stringent test of naive pluripotency.
