Document Detail


Reprogramming of telomeric regions during the generation of human induced pluripotent stem cells and subsequent differentiation into fibroblast-like derivatives.
MedLine Citation:
PMID:  20861676     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human induced pluripotent stem (hiPS) cells provide therapeutic promises, as well as a potent in vitro model for studying biological processes which take place during human embryonic development and subsequent differentiation in normal and disease states. The epigenetic characteristics of iPS cells are reprogrammed to the embryonic state at which they acquire pluripotency. In addition, telomeres in hiPS cell must elongate sufficiently to provide the necessary replicative potential. Recent studies have demonstrated that the epigenetic characteristics of telomeric and subtelomeric regions are pivotal in regulating telomere length. Here we study telomere length, subtelomeric DNA methylation and telomeric-repeat-containing RNA (TERRA) expression in several hiPS cell clones derived from normal neonatal foreskin fibroblasts. We find that telomeres lengthen significantly in hiPS cells in comparison to the parental fibroblast source, and progressively shorten after differentiation back into fibroblast-like cells, concomitantly with telomerase activation and down-regulation, respectively. Subtelomeres in hiPS cells were found to be generally hypermethylated in comparison to the parental source. However bisulfite analysis revealed that at several subtelomeres examined, methylation levels differed between hiPS clones and that both de novo methylation and demethylation processes occurred during telomere reprogramming. Notably, although subtelomeres were in general very highly methylated, TERRA levels were elevated in hiPS cells, albeit to different degrees in the various clones. TERRA elevation may reflect enhanced stability or impaired degradation in hiPS cells, and/or alternatively, increased transcription from the hypomethylated subtelomeres. We suggest that TERRA may play a role in regulation of appropriate telomere function and length in hiPS cells.
Authors:
Shiran Yehezkel; Annie Rebibo-Sabbah; Yardena Segev; Maty Tzukerman; Rony Shaked; Irit Huber; Lior Gepstein; Karl Skorecki; Sara Selig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  6     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-04-25     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  63-75     Citation Subset:  IM    
Affiliation:
Molecular Medicine Laboratory, Faculty of Medicine and Research Institute, Rambam Health Care Campus and Rappaport, Technion - Israel Institute of Technology, Haifa, Israel.
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MeSH Terms
Descriptor/Qualifier:
Cell Dedifferentiation / physiology*
Cell Differentiation / physiology*
Cells, Cultured
DNA Methylation / physiology
Fibroblasts / cytology,  metabolism*
Humans
Induced Pluripotent Stem Cells / cytology,  metabolism*
Male
Models, Biological*
Telomere / metabolism*
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