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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

Gene expression profiles of CTAs in mouse ES, EG, and EC cells and in mouse germ line cells. (a) Pluripotent ES and EG cells and ipotent EC cells express alkaline phosphatase and Oct4 and develop EBs; ES and EG cells differentiate into derivatives of three germ layers in teratomas (TES, TEG) while EC cells grow in vivo as malignant tumors (TEC). Scale bar equal 100 μm. (b) Expression of CTAs, Oct4, and Nanog in mouse ES, EG, and EC cells and EBs. (c) CTA expression profiles of germ line cells isolated from embryos of E 7.5, E 11.5 and E 14.5 stages.
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fig5: Gene expression profiles of CTAs in mouse ES, EG, and EC cells and in mouse germ line cells. (a) Pluripotent ES and EG cells and ipotent EC cells express alkaline phosphatase and Oct4 and develop EBs; ES and EG cells differentiate into derivatives of three germ layers in teratomas (TES, TEG) while EC cells grow in vivo as malignant tumors (TEC). Scale bar equal 100 μm. (b) Expression of CTAs, Oct4, and Nanog in mouse ES, EG, and EC cells and EBs. (c) CTA expression profiles of germ line cells isolated from embryos of E 7.5, E 11.5 and E 14.5 stages.

Mentions: The murine Mage genes, like their human homologues, are expressed in a wide variety of tumors, in fetal and adult male gonads, and in several embryonic and extraembryonic tissues [52–57]. In order to determine whether specific expression patterns of Mage-a and Mage-b genes can be attributed to pluripotent stem cell differentiation, CTA expression profiles were examined in mouse pluripotent stem cells (ES and EG cells) and embryonal teratocarcinoma cells (Figures 5(a) and 5(b)). Moreover, we compared them with the profiles of mouse primordial germ cells at the critical stages of germ line development: epiblast cells at early gastrulation stage, postmigratory primordial germ cells just after their occupation of developing genital ridges and gonocytes of male embryonic gonads. Our results suggest that the pluripotent ES and EG cells, ipotent teratocarcinoma EC cells and their EB cells expressed Mage-a1, 2, 3, 5, 6, 8 and Mage-d1, -d2 but did not express CTAs of Mage-b family. Furthermore, the expression of Magea-4 gene was detected in EGC-10 and EC F9 cells but not in ES R1 cells (Figure 5(b)).


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)

Gene expression profiles of CTAs in mouse ES, EG, and EC cells and in mouse germ line cells. (a) Pluripotent ES and EG cells and ipotent EC cells express alkaline phosphatase and Oct4 and develop EBs; ES and EG cells differentiate into derivatives of three germ layers in teratomas (TES, TEG) while EC cells grow in vivo as malignant tumors (TEC). Scale bar equal 100 μm. (b) Expression of CTAs, Oct4, and Nanog in mouse ES, EG, and EC cells and EBs. (c) CTA expression profiles of germ line cells isolated from embryos of E 7.5, E 11.5 and E 14.5 stages.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Gene expression profiles of CTAs in mouse ES, EG, and EC cells and in mouse germ line cells. (a) Pluripotent ES and EG cells and ipotent EC cells express alkaline phosphatase and Oct4 and develop EBs; ES and EG cells differentiate into derivatives of three germ layers in teratomas (TES, TEG) while EC cells grow in vivo as malignant tumors (TEC). Scale bar equal 100 μm. (b) Expression of CTAs, Oct4, and Nanog in mouse ES, EG, and EC cells and EBs. (c) CTA expression profiles of germ line cells isolated from embryos of E 7.5, E 11.5 and E 14.5 stages.
Mentions: The murine Mage genes, like their human homologues, are expressed in a wide variety of tumors, in fetal and adult male gonads, and in several embryonic and extraembryonic tissues [52–57]. In order to determine whether specific expression patterns of Mage-a and Mage-b genes can be attributed to pluripotent stem cell differentiation, CTA expression profiles were examined in mouse pluripotent stem cells (ES and EG cells) and embryonal teratocarcinoma cells (Figures 5(a) and 5(b)). Moreover, we compared them with the profiles of mouse primordial germ cells at the critical stages of germ line development: epiblast cells at early gastrulation stage, postmigratory primordial germ cells just after their occupation of developing genital ridges and gonocytes of male embryonic gonads. Our results suggest that the pluripotent ES and EG cells, ipotent teratocarcinoma EC cells and their EB cells expressed Mage-a1, 2, 3, 5, 6, 8 and Mage-d1, -d2 but did not express CTAs of Mage-b family. Furthermore, the expression of Magea-4 gene was detected in EGC-10 and EC F9 cells but not in ES R1 cells (Figure 5(b)).

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