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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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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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Journal Article
Human endogenous retrovirus K (HML-2) RNA and protein expression is a marker for human embryonic and induced pluripotent stem cells
2013
Overview
Background
Malignant human embryonal carcinoma cells (ECCs) rely on similar transcriptional networks as non-malignant embryonic stem cells (ESCs) 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 RT-PCR 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 ESCs and iPSCs 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(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 iPSCs.
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V
Subject
/ Benign
/ Biomedical and Life Sciences
/ Endogenous Retroviruses - genetics
/ Endogenous Retroviruses - physiology
/ Human endogenous retrovirus K
/ Humans
/ Induced Pluripotent Stem Cells - virology
/ Proteins
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA
/ RNA, Viral - isolation & purification
/ Vaccine
/ Virology
