Telomere Elongation and Naive Pluripotent Stem Cells Achieved from Telomerase Haplo-Insufficient Cells by Somatic Cell Nuclear Transfer
Author(s) -
LiYing Sung,
Wei-Fang Chang,
Qian Zhang,
Chia-Chia Liu,
JunYang Liou,
ChiaChun Chang,
Huan Ouyang,
Renpeng Guo,
Haifeng Fu,
Winston Teng-Kuei Cheng,
ShihTorng Ding,
ChuanMu Chen,
Maja Okuka,
David L. Keefe,
Y. Eugene Chen,
Lin Liu,
Jie Xu
Publication year - 2014
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2014.10.052
Subject(s) - telomerase , telomere , somatic cell , induced pluripotent stem cell , microbiology and biotechnology , stem cell , somatic cell nuclear transfer , elongation , biology , chemistry , genetics , embryonic stem cell , dna , gene , embryo , blastocyst , embryogenesis , materials science , ultimate tensile strength , metallurgy
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom