title: Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells.
abstract: Although somatic cell nuclear transfer (SCNT) and induction of pluripotency (to form iPSCs) are both recognized reprogramming methods, there has been relatively little comparative analysis of the resulting pluripotent cells. Here, we examine the capacity of these two reprogramming approaches to rejuvenate telomeres using late-generation telomerase-deficient (Terc(-/-)) mice that exhibit telomere dysfunction and premature aging. We found that embryonic stem cells established from Terc(-/-) SCNT embryos (Terc(-/-) ntESCs) have greater differentiation potential and self-renewal capacity than Terc(-/-) iPSCs. Remarkably, SCNT results in extensive telomere lengthening in cloned embryos and improved telomere capping function in the established Terc(-/-) ntESCs. In addition, mitochondrial function is severely impaired in Terc(-/-) iPSCs and their differentiated derivatives but significantly improved in Terc(-/-) ntESCs. Thus, our results suggest that SCNT-mediated reprogramming mitigates telomere dysfunction and mitochondrial defects to a greater extent than iPSC-based reprogramming. Understanding the basis of this differential could help optimize reprogramming strategies.
authors.affiliation: College of Biological Sciences, China Agricultural University, Beijing 100094, China; National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Le
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Kou
authors.affiliation: College of Biological Sciences, China Agricultural University, Beijing 100094, China; National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: College of Biological Sciences, China Agricultural University, Beijing 100094, China; National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Kou
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Wanzhong
authors.initials: W
authors.lastname: He
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena 07745, Germany.
authors.forename: Karl Lenhard
authors.initials: KL
authors.lastname: Rudolph
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China. Electronic address: zhenyuju@163.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ju
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing 102206, China; School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: gaoshaorong@tongji.edu.cn.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D054258:Neural Plate / Q000378:metabolism / Q000473:pathology; D053652:Nuclear Transfer Techniques; D012313:RNA / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C422952:telomerase RNA; D012313:RNA; D000255:Adenosine Triphosphate; D019098:Telomerase