title: The role of telomeres and telomerase reverse transcriptase isoforms in pluripotency induction and maintenance.
abstract: Telomeres are linear guanine-rich DNA structures at the ends of chromosomes. The length of telomeric DNA is actively regulated by a number of mechanisms in highly proliferative cells such as germ cells, cancer cells, and pluripotent stem cells. Telomeric DNA is synthesized by way of the ribonucleoprotein called telomerase containing a reverse transcriptase (TERT) subunit and RNA component (TERC). TERT is highly conserved across species and ubiquitously present in their respective pluripotent cells. Recent studies have uncovered intricate associations between telomeres and the self-renewal and differentiation properties of pluripotent stem cells. Interestingly, the past decade's work indicates that the TERT subunit also has the capacity to modulate mitochondrial function, to remodel chromatin structure, and to participate in key signaling pathways such as the Wnt/β-catenin pathway. Many of these non-canonical functions do not require TERT's catalytic activity, which hints at possible functions for the extensive number of alternatively spliced TERT isoforms that are highly expressed in pluripotent stem cells. In this review, some of the established and potential routes of pluripotency induction and maintenance are highlighted from the perspectives of telomere maintenance, known TERT isoform functions and their complex regulation.
authors.affiliation: a Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry , The University of Western Ontario , London , Ontario , Canada.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Teichroeb
authors.affiliation: a Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry , The University of Western Ontario , London , Ontario , Canada.
authors.forename: Joohwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: a Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry , The University of Western Ontario , London , Ontario , Canada.|b Children's Health Research Institute, Lawson Health Research Institute , London , Ontario , Canada.
authors.forename: Dean H
authors.initials: DH
authors.lastname: Betts
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015415:Biomarkers; D000066673:Cell Self Renewal / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D019098:Telomerase
keywords: Alternative splicing; TERT; embryonic stem cells; hESC; iPSC; pluripotency; telomerase; telomere