Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells.
Telomere shortening is associated with organismal aging. iPS cells have been recently derived from old patients; however, it is not known whether telomere chromatin acquires the same characteristics as in ES cells. We show here that telomeres are elongated in iPS cells compared to the parental differentiated cells both when using four (Oct3/4, Sox2, Klf4, cMyc) or three (Oct3/4, Sox2, Klf4) reprogramming factors and both from young and aged individuals. We demonstrate genetically that, during reprogramming, telomere elongation is usually mediated by telomerase and that iPS telomeres acquire the epigenetic marks of ES cells, including a low density of trimethylated histones H3K9 and H4K20 and increased abundance of telomere transcripts. Finally, reprogramming efficiency of cells derived from increasing generations of telomerase-deficient mice shows a dramatic decrease in iPS cell efficiency, a defect that is restored by telomerase reintroduction. Together, these results highlight the importance of telomere biology for iPS cell generation and functionality.
Marion
Rosa M
RM
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernández Almagro 3, Madrid, Spain.
Strati
Katerina
K
Li
Han
H
Tejera
Agueda
A
Schoeftner
Stefan
S
Ortega
Sagrario
S
Serrano
Manuel
M
Blasco
Maria A
MA
D000375:Aging / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D018183:Transplantation Chimera
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D016271:Proto-Oncogene Proteins c-myc; D019098:Telomerase