Telomere elongation and naive pluripotent stem cells achieved from telomerase haplo-insufficient cells by somatic cell nuclear transfer.
Journal
Cell reports
Journal Volume
9
Journal Issue
5
Start Page
1603
End Page
1609
ISSN
2211-1247
Date Issued
2014-12-11
Author(s)
Chang, Wei-Fang
Zhang, Qian
Liu, Chia-Chia
Liou, Jun-Yang
Ou-Yang, Huan
Guo, Renpeng
Fu, Haifeng
Cheng, Winston T K
Chen, Chuan-Mu
Okuka, Maja
Keefe, David L
Chen, Y Eugene
Liu, Lin
Xu, Jie
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.
Type
journal article