Telomere Reprogramming and Maintenance in Porcine iPS Cells
Open Access
- 30 September 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (9), e74202
- https://doi.org/10.1371/journal.pone.0074202
Abstract
Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells.Keywords
This publication has 72 references indexed in Scilit:
- Conservation and characterization of unique porcine interstitial telomeric sequencesScience China Life Sciences, 2012
- The Promise and Perils of Stem Cell TherapeuticsCell Stem Cell, 2012
- The Transcriptional and Epigenomic Foundations of Ground State PluripotencyCell, 2012
- Genetic modifications of pigs for medicine and agricultureMolecular Reproduction and Development, 2011
- Mammalian 5′ C-Rich Telomeric Overhangs Are a Mark of Recombination-Dependent Telomere MaintenanceMolecular Cell, 2011
- Mammalian Telomeres Resemble Fragile Sites and Require TRF1 for Efficient ReplicationCell, 2009
- A Method to Generate Genetically Defined Tumors in PigsMethods in Enzymology, 2008
- Defining Molecular Cornerstones during Fibroblast to iPS Cell Reprogramming in MouseCell Stem Cell, 2008
- Sequential Expression of Pluripotency Markers during Direct Reprogramming of Mouse Somatic CellsCell Stem Cell, 2008
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007