Cell‐surface antigens of a clonal human embryonal carcinoma cell line: Morphological and antigenic differentiation in culture

Andrews, Peter W.; Goodfellow, Peter N.; Shevinsky, L H; Bronson, David L.; Knowles, Barbara B.

doi:10.1002/ijc.2910290507

Cited by 182 publications

(72 citation statements)

References 39 publications

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“…Shef5 was derived at the University of Sheffield and became adapted as described in [8]. NTERA2 cl.D1, 1777Nrpmet, 2102Ep, 1156QE, and TERA-1 were derived from testicular teratocarcinomas [18][19][20][21][22], while human embryonal carcinoma cell line (NCCIT) was derived from an extragonadal germ cell tumor [23]. HCT116 is from American Type Culture Collection (Manassas, VA, www.atcc.org).…”

Section: Cell Linesmentioning

confidence: 99%

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

et al. 2012

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Pluripotent cells of the early embryo, to which embryonic stem cells (ESCs) correspond, give rise to all the somatic cells of the developing fetus. Any defects that occur in their genome or epigenome would have devastating consequences. Genetic and epigenetic change in human ESCs appear to be an inevitable consequence of long-term culture, driven by selection of variant cells that have a higher propensity for self-renewal rather than either differentiation or death. Mechanisms underlying the potentially separate events of mutation and subsequent selection of variants are poorly understood. Here, we show that human ESCs and their malignant counterpart, embryonal carcinoma (EC) cells, both fail to activate critical S-phase checkpoints when exposed to DNA replication inhibitors and commit to apoptosis instead. Human ESCs and EC cells also fail to form replication protein A, cH2AX, or RAD51 foci or load topoisomerase (DNA) II binding protein 1 onto chromatin in response to replication inhibitors. Furthermore, direct measurements of single-stranded DNA (ssDNA) show that these cells fail to generate the ssDNA regions in response to replication stress that are necessary for the activation of checkpoints and the initiation of homologous recombination repair to protect replication fork integrity and restart DNA replication. Taken together, our data suggest that pluripotent cells control genome integrity by the elimination of damaged cells through apoptosis rather than DNA repair, and therefore, mutations or epigenetic modifications resulting in an imbalance in cell death control could lead to genetic instability.

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Section: Cell Linesmentioning

confidence: 99%

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

et al. 2012

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“…23 To test whether nullipotent human EC cells fail to differentiate because of such a loss of function, or because they have acquired a mutation that actively inhibits differentiation, we have now investigated the properties of hybrids of the 2 human EC cell lines, 2102Ep and NTERA2, both derived from testicular germ cell tumors. The results suggest that the failure of 2102Ep cells to respond to retinoic acid, 10 and their failure to differentiate in xenografts 17,18 is also due to the loss of function of a key gene(s) rather than the gain of function of an inhibitor of differentiation. On the other hand, the hybrid cells do not appear to differentiate into neurons, as do the parent NTERA2 cells, 12 suggesting that 2102Ep cells may also have acquired inhibitory mutations relevant to this specific pathway of differentiation.…”

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confidence: 97%

“…16 For example, 2102Ep is a well-characterized, prototypical human EC cell line that forms xenograft tumors comprising only pure embryonal carcinoma with no other differentiated cell types in athymic (nu/nu) mice. 17,18 In culture, 2102Ep cells do not differentiate when exposed to retinoic acid, 16 although they undergo a rather limited form of morphological differentiation with some antigenic changes when grown at low cell density. 18 Among EC cell lines derived from teratocarcinomas of the laboratory mouse, some similarly retain a capacity for differentiation, while others do not.…”

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confidence: 99%

“…17,18 In culture, 2102Ep cells do not differentiate when exposed to retinoic acid, 16 although they undergo a rather limited form of morphological differentiation with some antigenic changes when grown at low cell density. 18 Among EC cell lines derived from teratocarcinomas of the laboratory mouse, some similarly retain a capacity for differentiation, while others do not. 19 A number of studies have been made of hybrids produced by the fusion of murine EC cells and differentiated somatic cells taken from adult mice, or from established murine cell lines (e.g., references 20 -26).…”

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confidence: 99%

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Hybrids of pluripotent and nullipotent human embryonal carcinoma cells: Partial retention of a pluripotent phenotype

et al. 2001

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To investigate whether the failure of human EC cells that do not differentiate is due to the loss of key differentiationpermissive functions or the acquisition of specific inhibitory functions, we tested the ability to differentiate of 2 hybrids produced between a relatively nullipotent human EC cell line, 2102Ep, and a pluripotent human EC cell line NTERA2. Both hybrids, which exhibited an EC phenotype, were able to differentiate readily in response to retinoic acid. Furthermore, 1 hybrid produced a well-differentiated xenograft tumor, which contained, like the NTERA2 tumors, glandular structures, loose mesenchymal tissues and nodules of cartilage, after injection into a SCID mouse. Thus, the failure of 2102Ep EC cells to differentiate is recessive and due to the loss of a key gene function or functions. Nevertheless, the hybrids differed from the pluripotent NTERA2 line by failing to differentiate in neurons, indicating that 2102Ep cells also had acquired a specific, dominantly-acting, inhibitory mutation specific to the neural lineage. Furthermore, the expression of collagen II by one hybrid before and after induction with retinoic suggested a propensity for spontaneous differentiation not evident in the parental NTERA2 cells. Thus, the mechanisms that restrict the differentiation capacity of the nullipotent 2102Ep line are complex and include both recessive and dominant acting factors.

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“…Definition of human teratocarcinoma stem cell morphology and expression of the stage-specific embryonic antigens SSEA-3 and SSEA-4 (but not SSEA-1) [119][120][121] prepared the way for Thomson and coworkers to isolate human ES cells from human blastocysts in 1998 [118]. These cells demonstrated the ability to form trophoblasts and derivatives of all three embryonic germ layers in teratomas after injection into immunodeficient mice.…”

Section: Non-mouse Stem Cellsmentioning

confidence: 99%

Technical Assessment of the First 20 Years of Research Using Mouse Embryonic Stem Cell Lines

Downing

Battey

2004

STEM CELLS

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This review assesses the effect that mouse embryonic stem (ES) cells have had on biomedical research during the 20 years that followed their isolation in 1981. Notable scientific discoveries enabled by these cell lines-including insights into cell cycle regulation, spatial and temporal relationships during development, and the roles of transcription factors and homeobox genes in developmental pathways-are discussed. The acceleration of basic discovery of gene function and the genetic basis of disease using a breakthrough technology (homologous recombination between modified gene constructs and the ES cell genome) became the principal enabling method to establish transgenic laboratory animals with single targeted genetic change. This review also examines the widespread influence of mouse ES cells as an enabling technology by highlighting their effect on drug development paradigms, directed differentiation to treat specific diseases, nuclear transfer protocols used in cloning, and establishment of methodologies for isolating non-rodent ES cells. This review concludes with a brief analysis of the most influential mouse ES cell lines of the first 20 years as viewed within the twin contexts of human disease application and contributions to the primary literature. Stem

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Cell‐surface antigens of a clonal human embryonal carcinoma cell line: Morphological and antigenic differentiation in culture

Cited by 182 publications

References 39 publications

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

Hybrids of pluripotent and nullipotent human embryonal carcinoma cells: Partial retention of a pluripotent phenotype

Technical Assessment of the First 20 Years of Research Using Mouse Embryonic Stem Cell Lines

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