The Aberrant DNA Methylation Profile of Human Induced Pluripotent Stem Cells Is Connected to the Reprogramming Process and Is Normalized During In Vitro Culture
Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
27336948
PubMed Central
PMC4919089
DOI
10.1371/journal.pone.0157974
PII: PONE-D-16-07052
Knihovny.cz E-zdroje
- MeSH
- buněčná diferenciace genetika MeSH
- buněčné linie MeSH
- fibroblasty cytologie metabolismus MeSH
- indukované pluripotentní kmenové buňky cytologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- lidské embryonální kmenové buňky cytologie metabolismus MeSH
- metylace DNA * MeSH
- přeprogramování buněk genetika MeSH
- shluková analýza MeSH
- stanovení celkové genové exprese MeSH
- vývojová regulace genové exprese MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The potential clinical applications of human induced pluripotent stem cells (hiPSCs) are limited by genetic and epigenetic variations among hiPSC lines and the question of their equivalency with human embryonic stem cells (hESCs). We used MethylScreen technology to determine the DNA methylation profile of pluripotency and differentiation markers in hiPSC lines from different source cell types compared to hESCs and hiPSC source cells. After derivation, hiPSC lines compromised a heterogeneous population characterized by variable levels of aberrant DNA methylation. These aberrations were induced during somatic cell reprogramming and their levels were associated with the type of hiPSC source cells. hiPSC population heterogeneity was reduced during prolonged culture and hiPSCs acquired an hESC-like methylation profile. In contrast, the expression of differentiation marker genes in hiPSC lines remained distinguishable from that in hESCs. Taken together, in vitro culture facilitates hiPSC acquisition of hESC epigenetic characteristics. However, differences remain between both pluripotent stem cell types, which must be considered before their use in downstream applications.
Centre for Biomedical Image Analysis Faculty of Informatics Masaryk University Brno Czech Republic
International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic
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