Telomere Dynamics in Human Cells Reprogrammed to Pluripotency

Human induced pluripotent stem cells (IPSCs) have enormous potential in the development of cellular models of human disease and represent a potential source of autologous cells and tissues for therapeutic use. A question remains as to the biological age of IPSCs, in particular when isolated from old...

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Vydané v:PloS one Ročník 4; číslo 12; s. e8124
Hlavní autori: Suhr, Steven T., Chang, Eun Ah, Rodriguez, Ramon M., Wang, Kai, Ross, Pablo J., Beyhan, Zeki, Murthy, Shashanka, Cibelli, Jose B.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Public Library of Science 02.12.2009
Public Library of Science (PLoS)
Predmet:
Age
Aged
Aging
Analysis
Animal genetic engineering
Animal sciences
Autografts
Cancer
Cell culture
Cell Differentiation
Cell Line
Cell lines
Cellular Reprogramming - genetics
Chromosomes
Deoxyribonucleic acid
Developmental Biology/Aging
Developmental Biology/Cell Differentiation
Developmental Biology/Embryology
Developmental Biology/Stem Cells
DNA
Elongation
Embryo cells
Embryonic stem cells
Embryos
Explants
Fibroblasts
Fibroblasts - cytology
Fibroblasts - metabolism
Genetic Vectors - genetics
Genomes
Health aspects
Heterogeneity
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Laboratories
Lentivirus - genetics
Male
Microscopy, Phase-Contrast
Phenotype
Pluripotency
Skin
Somatic cells
Stem cell transplantation
Stem cells
Telomerase
Telomere - metabolism
Telomeres
Teratoma
Teratoma - pathology
Tissues
Zoology
United States > US
East Lansing Michigan
Michigan
ISSN:1932-6203, 1932-6203
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Shrnutí:Human induced pluripotent stem cells (IPSCs) have enormous potential in the development of cellular models of human disease and represent a potential source of autologous cells and tissues for therapeutic use. A question remains as to the biological age of IPSCs, in particular when isolated from older subjects. Studies of cloned animals indicate that somatic cells reprogrammed to pluripotency variably display telomere elongation, a common indicator of cell "rejuvenation." We examined telomere lengths in human skin fibroblasts isolated from younger and older subjects, fibroblasts converted to IPSCs, and IPSCs redifferentiated through teratoma formation and explant culture. In IPSCs analyzed at passage five (P5), telomeres were significantly elongated in 6/7 lines by >40% and approximated telomere lengths in human embryonic stem cells (hESCs). In cell lines derived from three IPSC-teratoma explants cultured to P5, two displayed telomeres shortened to lengths similar to input fibroblasts while the third line retained elongated telomeres. While these results reveal some heterogeneity in the reprogramming process with respect to telomere length, human somatic cells reprogrammed to pluripotency generally displayed elongated telomeres that suggest that they will not age prematurely when isolated from subjects of essentially any age.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Conceived and designed the experiments: STS EAC JC. Performed the experiments: STS EAC RMR SM. Analyzed the data: STS EAC RMR KW PJR ZB. Contributed reagents/materials/analysis tools: STS EAC RMR KW. Wrote the paper: STS EAC JC.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0008124