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Human endogenous retrovirus K (HML-2) RNA and protein expression is a marker for human embryonic and induced pluripotent stem cells

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Item Type:Article
Title:Human endogenous retrovirus K (HML-2) RNA and protein expression is a marker for human embryonic and induced pluripotent stem cells
Creators Name:Fuchs, N.V., Loewer, S., Daley, G.Q., Izsvák, Z., Löwer, J. and Löwer, R.
Abstract:BACKGROUND: Malignant human embryonal carcinoma cells (ECC) rely on similar transcriptional networks as non-malignant embryonic stem cells (ESC) to control selfrenewal, maintain pluripotency; and inhibit differentiation. Because re-activation of silenced HERV-K(HML-2) loci is a hallmark of ECCs, we asked if this HERV group was also reactivated in ESCs and induced pluripotent stem cells (iPSCs). FINDINGS: Using RTPCR and Western Blot, we demonstrate HERV-K(HML-2) RNA and protein expression in undifferentiated human ESCs and iPSCs. Induction of differentiation by embryoid body formation resulted in rapid silencing of HERV-K(HML-2) provirus expression. Sequencing analysis of a conserved region of the gag gene showed that proviral expression in undifferentiated cells represents at least 11 of the 66 nearly full length HERV-K(HML-2) loci, with slightly varying patterns in individual cell lines. These proviruses are human specific integrations and harbor promoter competent long terminal repeats (LTR5hs subgroup). We observed high mRNA levels of the NP9 and Gag encoding proviruses K101(chromosome 22q11.21) in all and K10(5q33.3) in most of the ECC, ESC, and iPSC lines tested, while K37(11q23.3) mRNA was detected only in ESCs and iPSCs. In addition, we detected expression of proviral mRNA encoding the RNA export adaptor Rec in all cell lines studied. Proviral mRNA originating from the K108(7p22.1) locus, which inter alia codes for functional Rec and Env proteins, was only reactivated in malignant ECC lines, not in benign ESCs or iPSC. CONCLUSIONS: HERV-K(HML-2) RNA and protein expression is a marker for pluripotent human stem cells. Initiation of differentiation results in rapid down-regulation. Further studies are needed to explore a putative functional role of HERV-K(HML-2) RNA and proteins in pluripotent stem cells.
Keywords:Human Embryonic Stem Cells, Induced Pluripotent Stem Cells, Activation of Human Endogenous Retrovirus K Proviruses, Embryoid Body Differentiation, Pluripotency Marker
Publisher:BioMed Central
Page Range:115
Date:24 October 2013
Official Publication:https://doi.org/10.1186/1742-4690-10-115
PubMed:View item in PubMed

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