Volume 21, No 5, May 2011
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 21 Issue 5, May 2011: 779-792
ORIGINAL ARTICLES
Association of telomere length with authentic pluripotency of ES/iPS cells
Junjiu Huang1,2,*, Fang Wang1,3,*, Maja Okuka2, Na Liu3, Guangzhen Ji3, Xiaoying Ye3, Bingfeng Zuo3, Minshu Li3, Ping Liang4, William W Ge5, John CM Tsibris2, David L Keefe2,6 and Lin Liu2,3
1School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China;
2Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33612, USA;
3College of Life Sciences, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin 300071, China;
4Department of Biological Sciences, Brock University, Ontario, Canada L2S 3A1;
5Department of Biomedical Informatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA;
6Department of Obstetrics and Gynecology, New York University Langone Medical Center, New York 10016, USA
Correspondence: Lin Liu, David L Keefe,(liutelom@yahoo.com; David.Keefe@nyumc.org)
Telomerase and telomeres are important for indefinite replication of stem cells. Recently, telomeres of somatic cells were found to be reprogrammed to elongate in induced pluripotent stem cells (iPSCs). The role of telomeres in developmental pluripotency in vivo of embryonic stem cells (ESCs) or iPSCs, however, has not been directly addressed. We show that ESCs with long telomeres exhibit authentic developmental pluripotency, as evidenced by generation of complete ESC pups as well as germline-competent chimeras, the most stringent tests available in rodents. ESCs with short telomeres show reduced teratoma formation and chimera production, and fail to generate complete ESC pups. Telomere lengths are highly correlated (r > 0.8) with the developmental pluripotency of ESCs. Short telomeres decrease the proliferative rate or capacity of ESCs, alter the expression of genes related to telomere epigenetics, down-regulate genes important for embryogenesis and disrupt germ cell differentiation. Moreover, iPSCs with longer telomeres generate chimeras with higher efficiency than those with short telomeres. Our data show that functional telomeres are essential for the developmental pluripotency of ESCs/iPSCs and suggest that telomere length may provide a valuable marker to evaluate stem cell pluripotency, particularly when the stringent tests are not feasible.
Cell Research (2011) 21:779-792. doi:10.1038/cr.2011.16; published online 1 February 2011
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