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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

CTA expression patterns in hES SC5, SC7, and SC3a cells and hEC PA-1 cells. (a) Activity of alkaline phosphatase and OCT4 in undifferentiated hES and hEC cells and in EBs formed by these cell lines. Scale bar = 100 μm. (b) Histological sections through teratomas and teratocarcinomas formed by hES and hEC cell lines. Cell derivatives of three germ layers were found in teratomas (TES) formed by hES cells and entirely cancer cells in teratocarcinomas (TEC). Scale bar = 100 μm. (c) Normal diploid karyotypes of hES SC5, SC7, and SC3a cells: SC5—46, XX; SC7—46, XY; SC3a—46, XX. (d) Expression of CTAs in hES SC5, SC7, and SC3a cells, hEC PA-1 cells and EBs formed by these cells.
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fig2: CTA expression patterns in hES SC5, SC7, and SC3a cells and hEC PA-1 cells. (a) Activity of alkaline phosphatase and OCT4 in undifferentiated hES and hEC cells and in EBs formed by these cell lines. Scale bar = 100 μm. (b) Histological sections through teratomas and teratocarcinomas formed by hES and hEC cell lines. Cell derivatives of three germ layers were found in teratomas (TES) formed by hES cells and entirely cancer cells in teratocarcinomas (TEC). Scale bar = 100 μm. (c) Normal diploid karyotypes of hES SC5, SC7, and SC3a cells: SC5—46, XX; SC7—46, XY; SC3a—46, XX. (d) Expression of CTAs in hES SC5, SC7, and SC3a cells, hEC PA-1 cells and EBs formed by these cells.

Mentions: Human ES cell lines SC5, SC7, and SC3a were recently derived and characterized as pluripotent stem cells by standard in vitro and in vivo assays [51] and (Figures 2(a)–2(c)). The cytogenetic analysis of these cell lines has shown that they retained normal diploid karyotypes during at least 30 passages: 46, XX for SC5 and SC3a, and 46, XY for SC7 (Figure 2(c)). However, the differentiation potential of these lines has been found to be different. Human ES cell lines SC5 and SC7 formed teratomas with derivatives of three germ layers (Figure 2(b)) while SC3a cells were more prone to differentiation in vitro and had restricted capacity to grow in teratomas.


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)

CTA expression patterns in hES SC5, SC7, and SC3a cells and hEC PA-1 cells. (a) Activity of alkaline phosphatase and OCT4 in undifferentiated hES and hEC cells and in EBs formed by these cell lines. Scale bar = 100 μm. (b) Histological sections through teratomas and teratocarcinomas formed by hES and hEC cell lines. Cell derivatives of three germ layers were found in teratomas (TES) formed by hES cells and entirely cancer cells in teratocarcinomas (TEC). Scale bar = 100 μm. (c) Normal diploid karyotypes of hES SC5, SC7, and SC3a cells: SC5—46, XX; SC7—46, XY; SC3a—46, XX. (d) Expression of CTAs in hES SC5, SC7, and SC3a cells, hEC PA-1 cells and EBs formed by these cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: CTA expression patterns in hES SC5, SC7, and SC3a cells and hEC PA-1 cells. (a) Activity of alkaline phosphatase and OCT4 in undifferentiated hES and hEC cells and in EBs formed by these cell lines. Scale bar = 100 μm. (b) Histological sections through teratomas and teratocarcinomas formed by hES and hEC cell lines. Cell derivatives of three germ layers were found in teratomas (TES) formed by hES cells and entirely cancer cells in teratocarcinomas (TEC). Scale bar = 100 μm. (c) Normal diploid karyotypes of hES SC5, SC7, and SC3a cells: SC5—46, XX; SC7—46, XY; SC3a—46, XX. (d) Expression of CTAs in hES SC5, SC7, and SC3a cells, hEC PA-1 cells and EBs formed by these cells.
Mentions: Human ES cell lines SC5, SC7, and SC3a were recently derived and characterized as pluripotent stem cells by standard in vitro and in vivo assays [51] and (Figures 2(a)–2(c)). The cytogenetic analysis of these cell lines has shown that they retained normal diploid karyotypes during at least 30 passages: 46, XX for SC5 and SC3a, and 46, XY for SC7 (Figure 2(c)). However, the differentiation potential of these lines has been found to be different. Human ES cell lines SC5 and SC7 formed teratomas with derivatives of three germ layers (Figure 2(b)) while SC3a cells were more prone to differentiation in vitro and had restricted capacity to grow in teratomas.

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