Abstract
Pluripotent stem cells can differentiate into various lineages but undergo genetic and epigenetic changes during long-term cultivation and, therefore, require regular monitoring. The expression patterns of cancer-testis antigens (CTAs) MAGE-A2, -A3, -A4, -A6, -A8, -B2, and GAGE were examined in undifferentiated human embryonic stem (hES) cells, their differentiated derivatives, teratocarcinoma (hEC) cells, and cancer cell lines of neuroectodermal and mesodermal origin. Undifferentiated hES cells and embryoid body cells expressed MAGE-A3, -A6, -A4, -A8, and GAGEs while later differentiated derivatives expressed only MAGE-A8 or MAGE-A4. Likewise, mouse pluripotent stem cells also express CTAs of Magea but not Mageb family. Despite similarity of the hES and hEC cell expression patterns, MAGE-A2 and MAGE-B2 were detected only in hEC cells but not in hES cells. Moreover, our analysis has shown that CTAs are aberrantly expressed in cancer cell lines and display low tissue specificity. The identification of CTA expression patterns in pluripotent stem cells and their derivatives may be useful for isolation of abnormally CTA-expressing cells to improve the safety of stem-cell based therapy.
Highlights
Two approaches for pluripotent stem cell line production have been developed
In order to clarify the possible role of cancer-testis antigens (CTAs) in lineage determination during early development and specificity of CTA expression during pathological tissue development, we have examined CTA expression patterns of MAGE A, B, D, and GAGE families in the pluripotent stem cells, their spontaneously differentiated cell derivatives, and cancer cell lines derived from tissues of neuroectodermal and mesodermal origin
We have shown that several CTAs, such as MAGE-A3, -A4, -A6, -A8, and GAGEs, are expressed in the undifferentiated human embryonic stem (hES) cells and early differentiated embryoid bodies (EBs) cells while only one gene of MAGE-A family was expressed in the later differentiated cell derivatives of hES cells, MAGE-A8 in the extraembryonic endoderm and mesenchymal cells and MAGE-A4 in the neuroectodermal progenitors
Summary
The traditional way consists in the isolation of pluripotent cells from preimplantation embryos or the conversion of embryonic germ line cells into pluripotent stem cells [1,2,3,4] Another approach is experimental genome reprogramming of somatic cells to change their differentiation potential. Comparative analysis of numerous derived human embryonic stem (hES) cell lines demonstrated that they differed in cell growth rate, gene expression profiles, gene methylation profiles, and microRNA profiles [8,9,10]. The variation of transcriptional and gene methylation profiles of human ES and iPS cell lines has been widely discussed [18,19,20,21,22,23,24]
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