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

doi:10.1016/j.celrep.2014.10.052

Telomere elongation and naive pluripotent stem cells achieved from telomerase haplo-insufficient cells by somatic cell nuclear transfer

Cell Rep. 2014 Dec 11;9(5):1603-1609. doi: 10.1016/j.celrep.2014.10.052. Epub 2014 Nov 20.

Authors

Li-Ying Sung¹, Wei-Fang Chang², Qian Zhang³, Chia-Chia Liu⁴, Jun-Yang Liou⁵, Chia-Chun Chang², Huan Ou-Yang², Renpeng Guo³, Haifeng Fu³, Winston T K Cheng⁶, Shih-Torng Ding², Chuan-Mu Chen⁷, Maja Okuka⁸, David L Keefe⁹, Y Eugene Chen¹⁰, Lin Liu¹¹, Jie Xu¹²

Affiliations

¹ 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.
² Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC.
³ 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.
⁴ Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC; Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350 Taiwan, ROC.
⁵ Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350 Taiwan, ROC.
⁶ Institute of Biotechnology, National Taiwan University, Taipei, 106 Taiwan, ROC; Department of Animal Science and Biotechnology, Tunghai University, Taichung, 407 Taiwan, ROC.
⁷ 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.
⁸ Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33612, USA.
⁹ Department of Obstetrics and Gynecology, New York University Langone Medical Center, New York, NY 10016, USA.
¹⁰ Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
¹¹ 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.
¹² Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address: jiex@umich.edu.

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.

MeSH terms

Animals
Cell Differentiation
Cells, Cultured
Female
Haploinsufficiency
Induced Pluripotent Stem Cells / enzymology*
Male
Mice, Inbred C57BL
Mice, Knockout
Nuclear Transfer Techniques
Telomerase / genetics
Telomere / genetics*
Telomere Homeostasis

Substances

Telomerase

Associated data

GEO/GSE62692

Grants and funding

R03 HD053066/HD/NICHD NIH HHS/United States