CD 30 is a marker of undifferentiated human embryonic stem cells rather than a biomarker of transformed hESCs

Lagarkova, Maria A.; Volchkov, Pavel; Philonenko, Elena S.; Pfannkuche, Kurt; Prokhorovich, Maria A.; Заботина, Т. Н.; Hescheler, Juergen; Киселев, С. Л.

doi:10.4161/cc.7.22.6981

Cited by 13 publications

(10 citation statements)

References 8 publications

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“…The expression of CD30 correlated with activated NF‐κB and increased resistance to apoptosis. Subsequently, several reports show that expression of CD30 is not restricted to aneuploid hESCs [26–29]. Our data demonstrating that CD30 expression is induced by the serum‐free KOSR culture medium and that ascorbate is the specific compound in this medium responsible for CD30 expression now provide a rationale for these observations.…”

Section: Discussionsupporting

confidence: 71%

“…In our laboratory, every cell line cultured in KOSR expresses CD30 (HES2, HES3, HES4, MEL1, and MEL2). We and others have observed that CD30 expression is quickly downregulated on differentiation [25, 27, 28]. Therefore, CD30 has been put forward as a novel potential pluripotent stem cell marker (Drukker M, oral presentation at the Annual Meeting of International Society for Stem Cell Research 2006 and Lagarkova et al [27]).…”

Section: Discussionmentioning

confidence: 99%

“…Expression of CD30 activates NF‐κB signaling and protects hESCs from apoptosis [25]. Several groups subsequently reported CD30 expression in diploid hESCs [26–29]. The cause and long‐term biological consequences of CD30 expression in hESCs remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Ascorbate Promotes Epigenetic Activation of CD30 in Human Embryonic Stem Cells

et al. 2010

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Human embryonic stem cells (hESCs) and induced pluripotent stem cells have the ability to adapt to various culture conditions. Phenotypic and epigenetic changes brought about by the culture conditions can, however, have significant impacts on their use in research and in clinical applications. Here, we show that diploid hESCs start to express CD30, a biomarker for malignant cells in Hodgkin's disease and embryonal carcinoma cells, when cultured in knockout serum replacement (KOSR)-based medium, but not in fetal calf serum containing medium. We identify the commonly used medium additive, ascorbate, as the sole medium component in KOSR responsible for CD30 induction. Our data show that this epigenetic activation of CD30 expression in hESCs by ascorbate occurs through a dramatic loss of DNA methylation of a CpG island in the CD30 promoter. Analysis of the phenotype and transcriptome of hESCs that overexpress the CD30 signaling domain reveals that CD30 signaling leads to inhibition of apoptosis, enhanced single-cell growth, and transcriptome changes that are associated with cell signaling, lipid metabolism, and tissue development. Collectively, our data show that hESC culture media that contain ascorbate trigger CD30 expression through an epigenetic mechanism and that this provides a survival advantage and transcriptome changes that may help adapt hESCs to in vitro culture conditions.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

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Ascorbate Promotes Epigenetic Activation of CD30 in Human Embryonic Stem Cells

et al. 2010

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“…Nevertheless, these sublines retained many basic characteristics of hESCs, including expression of Oct-4, SSEA-4, alkaline phosphatase, and a number of other specific markers. No differences in CD30 expression were found between karyotypically normal and abnormal cell lines (Lagarkova et al 2008a). At the same time, reduced capacity for spontaneous differentiation of hESM01r18 and hESM03der9 cells and delayed formation of embryoid bodies by hESM01r18 cells have been observed.…”

Section: Resultsmentioning

confidence: 85%

Human embryonic stem cell lines isolation, cultivation, and characterization

Lagarkova

Eremeev²,

Светлаков³

et al. 2010

In Vitro Cell.Dev.Biol.-Animal

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A large number of human embryonic stem cell (hESC) lines have been derived worldwide since the first hESC line establishment in 1998. Despite many common characteristics, most important of which is the pluripotency, hESC lines vary significantly in their transcriptional profiles, genetic, and epigenetic state. These differences may arise both from individual genetics of the cell lines and from variations in their handling such as isolation and cultivation. In order to minimize the latter differences, the standardized protocols of cultivation and inter-laboratory comprehensive studies should be performed. In this report, we summarized our experience of derivation and characterization of hESC lines as well as of adaptation of hESCs to novel cultivation protocols. We have successfully derived five hESC lines and characterized them by previously established criteria, including expression of specific markers and the capacity to differentiate both in vitro and in vivo. Four of these lines, namely hESM01-04, were initially derived using mouse fibroblasts as a feeder and currently are maintained under feeder-free, serum-free conditions using mTeSR1 and Matrigel. The fifth line, hESMK05 was derived in feeder-free, serum-free conditions using mTeSR1 and Matrigel. Cell lines retain their pluripotent status and normal karyotype for more than 70 passages and are available to the scientific community.

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“…However, growth conditions during clonogenic assays are markedly different from those during normal hESC culture, and it is possible that CD30 might have a specific effect on the regrowth of singlet cells. In this regard it notable that CD30 has recently been reported as marker of undifferentiated cells [18], such that in certain hESC lines it may act akin to, for example, SSEA3, in recognizing a pluripotent, clonogenic population rather than abnormal variants.…”

Section: Discussionmentioning

confidence: 99%

CD30 Expression Reveals that Culture Adaptation of Human Embryonic Stem Cells Can Occur Through Differing Routes

et al. 2009

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Human embryonic stem cells undergo adaptive changes that can increase their growth capacity upon prolonged culture in vitro. This is frequently associated with nonrandom karyotypic changes, commonly involving amplification of genetic material from chromosomes 12, 17, and X. A recent study suggested that the karyotypically abnormal cells can be identified by their expression of CD30, which confers resistance to apoptosis. We have now investigated CD30 expression and apoptosis in karyotypically normal and abnormal sublines of the human ES cell line, H7, but our results were contrary to those previously observed. In this cell line, CD30 expression did not segregate the normal and abnormal cells, and abnormal cells were not protected from apoptosis. These data suggest that culture adaptation can occur through a variety of mechanisms.

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CD 30 is a marker of undifferentiated human embryonic stem cells rather than a biomarker of transformed hESCs

Cited by 13 publications

References 8 publications

Ascorbate Promotes Epigenetic Activation of CD30 in Human Embryonic Stem Cells

Ascorbate Promotes Epigenetic Activation of CD30 in Human Embryonic Stem Cells

Human embryonic stem cell lines isolation, cultivation, and characterization

CD30 Expression Reveals that Culture Adaptation of Human Embryonic Stem Cells Can Occur Through Differing Routes

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