Embryonic stem cells and pluripotent germ cell tumors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE3921 | GEO | 2005/12/29
SECONDARY ACCESSION(S): PRJNA94175
REPOSITORIES: GEO
Similar Datasets
Project description:Exon-level transcriptome analysis of embryonal carcinoma (EC) and embryonic stem (ES) cell lines. To circumvent difficulties of isolating pure populations of cancer stem cells for the purpose of identifying malignancy-specific gene expression, we have compared exon-resolution transcriptomic profiles of five embryonal carcinoma (EC) cell lines, a histological subtype of germ cell tumour, to their non-malignant caricature, specifically six human embryonic stem (ES) cell lines. Both cell types are readily accessible, and were purified for undifferentiated cells only. We identified a set of 28 differentially expressed genes, many of which had cancer and stemness roles. Overexpression of the recently discovered pluripotency gene NR5A2 in malignant EC cells revealed an intriguing indication of how WNT-mediated dysregulation of pluripotency is involved with malignancy. At the exon-level, alternative splicing events were detected in ZNF195, DNMT3B and PMF1, and alternative promoters were detected for ASH2L and ETV5. These events were validated by RT-PCR-based methods in EC and ES lines, and further explored within a series of 25 primary tumours, where the alternative splicing event in the de novo DNA methyltransferase DNMT3B may have functional consequences. In conclusion, we have identified malignancy-specific gene expression differences within a rigorous pluripotent stem cell context. These findings are of particular interest for both germ cell tumour and ES cell biology, and in general to the concept of cancer stem cells.
2015-01-01 | GSE34855 | GEO
Project description:Exon-level transcriptome analysis of embryonal carcinoma (EC) and embryonic stem (ES) cell lines. To circumvent difficulties of isolating pure populations of cancer stem cells for the purpose of identifying malignancy-specific gene expression, we have compared exon-resolution transcriptomic profiles of five embryonal carcinoma (EC) cell lines, a histological subtype of germ cell tumour, to their non-malignant caricature, specifically six human embryonic stem (ES) cell lines. Both cell types are readily accessible, and were purified for undifferentiated cells only. We identified a set of 28 differentially expressed genes, many of which had cancer and stemness roles. Overexpression of the recently discovered pluripotency gene NR5A2 in malignant EC cells revealed an intriguing indication of how WNT-mediated dysregulation of pluripotency is involved with malignancy. At the exon-level, alternative splicing events were detected in ZNF195, DNMT3B and PMF1, and alternative promoters were detected for ASH2L and ETV5. These events were validated by RT-PCR-based methods in EC and ES lines, and further explored within a series of 25 primary tumours, where the alternative splicing event in the de novo DNA methyltransferase DNMT3B may have functional consequences. In conclusion, we have identified malignancy-specific gene expression differences within a rigorous pluripotent stem cell context. These findings are of particular interest for both germ cell tumour and ES cell biology, and in general to the concept of cancer stem cells. 5 EC and 6 ES cell lines gown on plastic and feeders respectively were sorted for the pluripotency marker SSEA3, then profiled on the Affymetrix Human Exon 1.0 ST platform. 3 additional EC lines grown on feeders and ES medium were also profiled in the same way. Data was analyzed using Qlucore (PCA), XRAY and limma (gene- and exon-level expression differences) and SAM (two-class pair-wise Significance of Microarrays).
2015-01-01 | E-GEOD-34855 | biostudies-arrayexpress
Project description:Background: Germ Cell Cancers (GCC), originating from Primordial Germ Cells /gonocytes, are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS, stem cell component: embryonal carcinoma (EC)). Somatic mutations are rarely found in GCC. It has been proposed that disruption of the epigenetic constitution, either primarily or secondary (e.g. environmental influences), is involved in cancer, and specifically in GCC. Results: This study aims at identifying epigenetic footprints of SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in GCC and related disruption of germ cell maturation. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data was acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP sequencing (activating histone modifications (H3K4me3, H3K27ac)). The data show that known germ cell markers are not only present and differentiating between SE and NS at the expression level, but also in the epigenetic landscape. Conclusion: The overall similarity between TCam-2 / NCCIT supports an erased embryonic gem cell arrested in early gonadal development as common origin. Subtle difference in the (integrated) epigenetic and expression profiles indicated TCam-2 to exhibit a more germ cell like profile (enrichment Androgen regulation) while NCCIT proved more pluripotent. The results provide insight into an integrated analysis of the functional genome in GCC cell lines. Two wildtype germ cell cancer (type II germ cell tumor) cell lines were analyzed. TCam-2 (representative for the seminomatous subtype of germ cell cancer) , [1, 2]) and NCCIT (representative of the non-seminomatous (embryonal carcinoma) subtype of germ cell cancer, [3]). 1. Mizuno, Y., et al., [Establishment and characterization of a new human testicular germ cell tumor cell line (TCam-2)]. Nihon Hinyokika Gakkai Zasshi, 1993. 84(7): p. 1211-8. 2. de Jong, J., et al., Further characterization of the first seminoma cell line TCam-2. Genes Chromosomes Cancer, 2008. 47(3): p. 185-96. 3. Teshima, S., et al., Four new human germ cell tumor cell lines. Lab Invest, 1988. 59(3): p. 328-36.
2014-06-01 | E-GEOD-56382 | biostudies-arrayexpress
Project description:Background: Germ Cell Cancers (GCC), originating from Primordial Germ Cells /gonocytes, are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS, stem cell component: embryonal carcinoma (EC)). Somatic mutations are rarely found in GCC. It has been proposed that disruption of the epigenetic constitution, either primarily or secondary (e.g. environmental influences), is involved in cancer, and specifically in GCC. Results: This study aims at identifying epigenetic footprints of SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in GCC and related disruption of germ cell maturation. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data was acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP sequencing (activating histone modifications (H3K4me3, H3K27ac)). The data show that known germ cell markers are not only present and differentiating between SE and NS at the expression level, but also in the epigenetic landscape. Conclusion: The overall similarity between TCam-2 / NCCIT supports an erased embryonic gem cell arrested in early gonadal development as common origin. Subtle difference in the (integrated) epigenetic and expression profiles indicated TCam-2 to exhibit a more germ cell like profile (enrichment Androgen regulation) while NCCIT proved more pluripotent. The results provide insight into an integrated analysis of the functional genome in GCC cell lines. Two wildtype germ cell cancer (type II germ cell tumor) cell lines were analyzed. TCam-2 (representative for the seminomatous subtype of germ cell cancer) , [1, 2]) and NCCIT (representative of the non-seminomatous (embryonal carcinoma) subtype of germ cell cancer, [3]). Of each cell line two biological replicates were included. 1. Mizuno, Y., et al., [Establishment and characterization of a new human testicular germ cell tumor cell line (TCam-2)]. Nihon Hinyokika Gakkai Zasshi, 1993. 84(7): p. 1211-8. 2. de Jong, J., et al., Further characterization of the first seminoma cell line TCam-2. Genes Chromosomes Cancer, 2008. 47(3): p. 185-96. 3. Teshima, S., et al., Four new human germ cell tumor cell lines. Lab Invest, 1988. 59(3): p. 328-36.
2014-06-01 | E-GEOD-56381 | biostudies-arrayexpress
Project description:Background: Germ Cell Cancers (GCC), originating from Primordial Germ Cells /gonocytes, are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS, stem cell component: embryonal carcinoma (EC)). Somatic mutations are rarely found in GCC. It has been proposed that disruption of the epigenetic constitution, either primarily or secondary (e.g. environmental influences), is involved in cancer, and specifically in GCC. Results: This study aims at identifying epigenetic footprints of SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in GCC and related disruption of germ cell maturation. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data was acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP sequencing (activating histone modifications (H3K4me3, H3K27ac)). The data show that known germ cell markers are not only present and differentiating between SE and NS at the expression level, but also in the epigenetic landscape. Conclusion: The overall similarity between TCam-2 / NCCIT supports an erased embryonic gem cell arrested in early gonadal development as common origin. Subtle difference in the (integrated) epigenetic and expression profiles indicated TCam-2 to exhibit a more germ cell like profile (enrichment Androgen regulation) while NCCIT proved more pluripotent. The results provide insight into an integrated analysis of the functional genome in GCC cell lines. Two wildtype germ cell cancer (type II germ cell tumor) cell lines were analyzed. TCam-2 (representative for the seminomatous subtype of germ cell cancer) , [1, 2]) and NCCIT (representative of the non-seminomatous (embryonal carcinoma) subtype of germ cell cancer, [3]). Of each cell line two biological replicates were included. Genomic positions reported are based on the GRch37/hg19 assembly. 1. Mizuno, Y., et al., [Establishment and characterization of a new human testicular germ cell tumor cell line (TCam-2)]. Nihon Hinyokika Gakkai Zasshi, 1993. 84(7): p. 1211-8. 2. de Jong, J., et al., Further characterization of the first seminoma cell line TCam-2. Genes Chromosomes Cancer, 2008. 47(3): p. 185-96. 3. Teshima, S., et al., Four new human germ cell tumor cell lines. Lab Invest, 1988. 59(3): p. 328-36.
2014-06-01 | E-GEOD-56450 | biostudies-arrayexpress
Project description:This study represents a proteomic resource for testis cancer with quantitative protein expression data for 5236 proteins. By quantitative mass-spectrometry-based proteomics, we compared the two Malignant germ cell tumour cell lines, TCam-2 with seminoma-like characteristics, and NTERA-2, an embryonal carcinoma-like cell line.
2019-11-12 | PXD010275 | Pride
Project description:Type II germ cell tumors (GCTs) are the most common neoplasia in young men of age 14-45 years. It is generally accepted that GCTs arise from a common precursor lesion, called germ cell neoplasia in situ (GCNIS), eventually developing into seminomas or non-seminomas, such as (embryonal carcinomas, ECs). The latter stem-cell like EC can further differentiate into teratomas (TE), yolk-sac tumors (YST), or choriocarcinomas (CC). Even though cisplatin-based chemotherapy is an efficacious standard of care during the management of GCT patients, the development of cisplatin resistance remains a major obstacle. As such, the surrounding tumor microenvironment and its secreted factors could endorse the development of drug resistance. These stromal cells, including immune cells (e.g. macrophages, T-lymphocytes), endothelial cells, and fibroblasts, can influence tumor cells by promoting proliferative and anti-apoptotic signaling pathways. Vice versa, microenvironmental cells can be influenced by tumor cells as well. For the identification of secreted proteins, cell lysates and supernatants from seven human germ cell tumor cell lines (seminoma: TCam-2; embryonal carcinoma (EC): 2102EP, NCCIT; choriocarcinoma (CC): JAR, JEG-3), yolk-sac tumor (YST): GCT72; 1411H) and five human cell types from the microenvironment (fibroblasts: MPAF, HVHF2; M2 macrophages: THP-1-M2; T-lymphocytes: JURKAT; endothelial cells: HUVEC) have been evaluated using liquid chromatography coupled with mass spectrometry (LC-MS).
2022-10-13 | PXD031329 | Pride
Project description:Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to insure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but as of yet not from humans. Here we analyzed a large collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics such as self-renewal capacity and a pluripotency-specific molecular signature. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Intriguingly, we found that a haploid genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics, development and evolution. RNA sequencing analysis was performed on a total of 2 samples of in vitro fertilization (IVF) control embryonic stem cell lines.
2016-03-16 | E-GEOD-74953 | biostudies-arrayexpress
Project description:Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to insure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but as of yet not from humans. Here we analyzed a large collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics such as self-renewal capacity and a pluripotency-specific molecular signature. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Intriguingly, we found that a haploid genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics, development and evolution.
2016-03-16 | GSE74953 | GEO
Project description:Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to insure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but as of yet not from humans. Here we analyzed a large collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics such as self-renewal capacity and a pluripotency-specific molecular signature. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Intriguingly, we found that a haploid genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics, development and evolution.
2016-03-16 | GSE71457 | GEO