title: Telomerase-mediated telomere elongation from human blastocysts to embryonic stem cells.
abstract: High telomerase activity is a characteristic of human embryonic stem cells (hESCs), however, the regulation and maintenance of correct telomere length in hESCs is unclear. In this study we investigated telomere elongation in hESCs in vitro and found that telomeres lengthened from their derivation in blastocysts through early expansion, but stabilized at later passages. We report that the core unit of telomerase, hTERT, was highly expressed in hESCs in blastocysts and throughout long-term culture; furthermore, this was regulated in a Wnt-β-catenin-signaling-dependent manner. Our observations that the alternative lengthening of telomeres (ALT) pathway was suppressed in hESCs and that hTERT knockdown partially inhibited telomere elongation, demonstrated that high telomerase activity was required for telomere elongation. We observed that chromatin modification through trimethylation of H3K9 and H4K20 at telomeric regions decreased during early culture. This was concurrent with telomere elongation, suggesting that epigenetic regulation of telomeric chromatin may influence telomerase function. By measuring telomere length in 96 hESC lines, we were able to establish that telomere length remained relatively stable at 12.02 ± 1.01 kb during later passages (15-95). In contrast, telomere length varied in hESCs with genomic instability and hESC-derived teratomas. In summary, we propose that correct, stable telomere length may serve as a potential biomarker for genetically stable hESCs.
authors: Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha 410001, China.
authors: Sicong
authors: S
authors: Zeng
authors: Lvjun
authors: L
authors: Liu
authors: Yi
authors: Y
authors: Sun
authors: Pingyuan
authors: P
authors: Xie
authors: Liang
authors: L
authors: Hu
authors: Ding
authors: D
authors: Yuan
authors: Dehua
authors: D
authors: Chen
authors: Qi
authors: Q
authors: Ouyang
authors: Ge
authors: G
authors: Lin
authors: Guangxiu
authors: G
authors: Lu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001755:Blastocyst / Q000201:enzymology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000201:enzymology*; D042822:Genomic Instability; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D009368:Neoplasm Transplantation; D011499:Protein Processing, Post-Translational; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis; D013724:Teratoma / Q000201:enzymology / Q000473:pathology; D060449:Wnt Signaling Pathway
chemical_list: D015415:Biomarkers; D002843:Chromatin; D006657:Histones; C509186:TERT protein, human; D019098:Telomerase
keywords: Embryonic stem cells; Telomerase; Telomere; Wnt–β-catenin signaling