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Expression patterns of cancer-testis antigens in human embryonic stem cells and their cell derivatives indicate lineage tracks.

Lifantseva N, Koltsova A, Krylova T, Yakovleva T, Poljanskaya G, Gordeeva O - Stem Cells Int (2011)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov Street, Moscow 119334, Russia.

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.

No MeSH data available.


Related in: MedlinePlus

Expression of CTAs and lineage-specific genes in differentiated hES cell derivatives. (a) Morphology and immunostaining of extraembryonic endoderm derivatives by antibodies against GATA4 and OCT4, mesenchymal cells against α-ACTININ and OCT4,  neuroectodermal cells against NESTIN and NANOG. Scale bar = 100 μm. (b) Expression profiles of CTAs and lineage marker genes in hES cell derivatives.
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fig3: Expression of CTAs and lineage-specific genes in differentiated hES cell derivatives. (a) Morphology and immunostaining of extraembryonic endoderm derivatives by antibodies against GATA4 and OCT4, mesenchymal cells against α-ACTININ and OCT4, neuroectodermal cells against NESTIN and NANOG. Scale bar = 100 μm. (b) Expression profiles of CTAs and lineage marker genes in hES cell derivatives.

Mentions: We studied three types of early differentiated cell derivatives of human ES SC5 and SC7 cells that predominated during spontaneous hES cell differentiation in vitro. These cells were easily distinguished from other cells in morphology and could be easily separated from other cells in cell outgrowths (Figure 3(a)). To identify cell types, we analyzed specific gene and protein expression in the studied samples. The expression of specific marker genes for pluripotent (OCT4, NANOG), extraembryonic endoderm (GATA4, AFP), neuroectodermal (NESTIN) and mesenchymal-like (BRY and α-Actinin) cells was tested by RT-PCR (Figure 3(b)) and immunohistochemical staining (Figure 3(a)). Analysis of CTA expression in these selected cell derivatives has shown that the extraembryonic endoderm cells expressing high levels of GATA4 and AFP and low level of OCT4 express MAGE-A8 and MAGE-D1, -D2 as well (Figure 3). Mesenchymal-like cells that were α-Actinin positive but BRY-negative had CTA expression profile similar to that of extraembryonic endoderm cells (Figure 3). In contrast, the neuroectodermal cell derivatives expressed NESTIN and MAGE-A4 (Figure 3). Moreover, all three cell types expressed MAGE-D1, -D2 genes and did not express GAGE genes.


Expression patterns of cancer-testis antigens in human embryonic stem cells and their cell derivatives indicate lineage tracks.

Lifantseva N, Koltsova A, Krylova T, Yakovleva T, Poljanskaya G, Gordeeva O - Stem Cells Int (2011)

Expression of CTAs and lineage-specific genes in differentiated hES cell derivatives. (a) Morphology and immunostaining of extraembryonic endoderm derivatives by antibodies against GATA4 and OCT4, mesenchymal cells against α-ACTININ and OCT4,  neuroectodermal cells against NESTIN and NANOG. Scale bar = 100 μm. (b) Expression profiles of CTAs and lineage marker genes in hES cell derivatives.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140037&req=5

fig3: Expression of CTAs and lineage-specific genes in differentiated hES cell derivatives. (a) Morphology and immunostaining of extraembryonic endoderm derivatives by antibodies against GATA4 and OCT4, mesenchymal cells against α-ACTININ and OCT4, neuroectodermal cells against NESTIN and NANOG. Scale bar = 100 μm. (b) Expression profiles of CTAs and lineage marker genes in hES cell derivatives.
Mentions: We studied three types of early differentiated cell derivatives of human ES SC5 and SC7 cells that predominated during spontaneous hES cell differentiation in vitro. These cells were easily distinguished from other cells in morphology and could be easily separated from other cells in cell outgrowths (Figure 3(a)). To identify cell types, we analyzed specific gene and protein expression in the studied samples. The expression of specific marker genes for pluripotent (OCT4, NANOG), extraembryonic endoderm (GATA4, AFP), neuroectodermal (NESTIN) and mesenchymal-like (BRY and α-Actinin) cells was tested by RT-PCR (Figure 3(b)) and immunohistochemical staining (Figure 3(a)). Analysis of CTA expression in these selected cell derivatives has shown that the extraembryonic endoderm cells expressing high levels of GATA4 and AFP and low level of OCT4 express MAGE-A8 and MAGE-D1, -D2 as well (Figure 3). Mesenchymal-like cells that were α-Actinin positive but BRY-negative had CTA expression profile similar to that of extraembryonic endoderm cells (Figure 3). In contrast, the neuroectodermal cell derivatives expressed NESTIN and MAGE-A4 (Figure 3). Moreover, all three cell types expressed MAGE-D1, -D2 genes and did not express GAGE genes.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov Street, Moscow 119334, Russia.

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.

No MeSH data available.


Related in: MedlinePlus