The Aberrant DNA Methylation Profile of Human Induced Pluripotent Stem Cells Is Connected to the Reprogramming Process and Is Normalized During In Vitro Culture

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TESAŘOVÁ Lenka ŠIMARA Pavel STEJSKAL Stanislav KRONTORÁD KOUTNÁ Irena

Rok publikování 2016
Druh Článek v odborném periodiku
Časopis / Zdroj PLOS ONE
Fakulta / Pracoviště MU

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Citace
www http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157974
Doi http://dx.doi.org/10.1371/journal.pone.0157974
Obor Genetika a molekulární biologie
Klíčová slova pluripotent stem cells; DNA methylation; MethylScreen technology; CpG islands; pluripotency and differentiation markers
Popis 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.
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