Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of human embryonic stem cells with features of neoplastic progression

ABSTRACT: Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced ‘stemness’. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization revealed an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b;5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE13995 | GEO | 2008/12/25

SECONDARY ACCESSION(S): PRJNA112493

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Characterization of human embryonic stem cells with features of neoplastic progression

Project description:Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced âstemnessâ. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization revealed an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b;5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells. Custom oligonucleotide array gene expression analysis was performed on total RNA from low passage normal and variant human embryonic stem cell (hESC) lines, all cultured in our laboratory under the same conditions. Furthermore, array-based comparative genomic hybridization was also performed on the normal and variant hESC lines. v-hESC-1 and v-hESC-2 represent two independent lines that display neoplastic characteristics with distinctive copy number alterations. v-hESC-1_A2B5 represents neural precursor cultures differentiated from variant hES cells. GSM349016-GSM349022: Gene expression analysis GSM351500-GSM351511: aCGH analysis

2010-06-24 | E-GEOD-13995 | biostudies-arrayexpress

Comparable mRNA expression of pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system

Project description:I developed a new culture system for hES cells; this system does not require supplementation with bFGF to obtain hES cells that are suitable for tissue engineering and regenerative medicine. This culture system employed mesenchymal stem cells derived from hES cells (hESC-MSCs) as autologous human feeder cells in the absence of bFGF. For pluripotency-related gene expression profiling, a cDNA microarray analysis was performed SNUhES3 cultured on the autofeeder hESC-MSCs layer maintained the undifferentiated state for 30 passages in a manner similar to the SNUhES3 cells on xenofeeder STO cell layer. To compare the pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system, I used agilent one-color array. Two independant experiment performed.

2011-02-02 | E-GEOD-26993 | biostudies-arrayexpress

Comparable mRNA expression of pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system

2011-02-02 | GSE26993 | GEO

Stirred suspension bioreactors maintain naïve pluripotency of human pluripotent stem cells (hPSCs)

Project description:Although cell therapies require large numbers of quality-controlled hPSCs, existing technologies are limited in their ability to efficiently grow and scale stem cells. We report here that cell-state conversion from primed-to-naïve pluripotency enhances the biomanufacturing of hPSCs. Naïve hPSCs exhibit superior growth kinetics and aggregate formation characteristics in stirred suspension bioreactors compared to their primed counterparts. Moreover, we demonstrate the role of the bioreactor mechanical environment in the maintenance of naïve pluripotency, through transcriptomic enrichment of mechano-sensing signaling for cells in the bioreactor along with a decrease in expression of lineage-specific and primed pluripotency hallmarks. Bioreactor-cultured, naïve hPSCs express epigenetic regulatory transcripts associated with naïve pluripotency, and display hallmarks of X-chromosome reactivation. They exhibit robust production of naïve pluripotency metabolites and display reduced expression of primed pluripotency cell surface markers. We also show that these cells retain the ability to undergo targeted differentiation into beating cardiomyocytes, hepatocytes, and neural rosettes. They additionally display faster kinetics of teratoma formation compared to their primed counterparts. Naïve bioreactor hPSCs also retain structurally stable chromosomes. Our research corroborates that converting hPSCs to the naïve state enhances hPSC manufacturing and indicates a potentially important role for the bioreactor’s mechanical environment in maintaining naïve pluripotency.

2020-05-08 | ST001377 | MetabolomicsWorkbench

Dmrt1 (doublesex and mab-3 related transcription factor 1) knockout expression analyses in E13.5 testes in S6 background

Project description:Dmrt1 (doublesex and mab-3 related transcription factor 1) is a conserved transcriptional regulator of male differentiation required for testicular development in vertebrates. In mice of the 129Sv strain, loss of Dmrt1 causes a high incidence of teratomas. Mutant 129Sv germ cells undergo apparently normal differentiation up to embryonic day 13.5 (E13.5), but some cells fail to arrest mitosis and ectopically express pluripotency markers. Expression analysis and chromatin immunoprecipitation identified DMRT1 target genes whose misexpression may underly teratoma formation. Comparison of E13.5 testes gene expression between Dmrt1(+/-) and Dmrt1(-,-) animals that show high incidence of teratoma formation.

2010-07-30 | E-GEOD-18396 | biostudies-arrayexpress

Molecular Insights into Non-teratoma-forming Induced Pluripotent Stem Cells

Project description:Human induced pluripotent stem (iPS) cells are capable of differentiating into derivatives of the three embryonic germ layers both in vitro and in vivo. To date the the molecular differences between teratoma-forming cells and non-teratoma-forming cells has not been analysed. A cell line, B1, bears typical ES cell-like morphology, expression of pluripotency-associated genes, and in vitro pluripotency capacity, but fails to form teratomas after subcutaneously injected into immune-deficient mice based on histological analysis. Besides histological analysis, we characterized the tumors derived from line B1, and teratomas derived from bona fida iPS and ES (line H1) cells respectively, using microarray-based gene expression analysis. The expression levels of pluripotency-associated markers in B1 cells were comparable to that in iPS and ES cells, while the complexity of tissue expression commitment was decreased upon spontaneous differentiation of B1 cells as compared to iPS and ES cells. Total RNA obtained from HFF1 (human foreskin fibroblast) cells, line B1, iPS-A4, iPS-B4 and ES (line H1) cells, and their derived tumors in immune-deficient mice.

2012-04-29 | E-GEOD-31970 | biostudies-arrayexpress

Transcription profiling of human liver-specific miR-122 overexpression on embryonic stem cells (hESC) differentiation

Project description:We aimed to determine whether overexpression of endoderm-specific miRNA may affect hESC differentiation. To this end, we analyzed the effect of lentiviral-based overexpression of liver-specific miR-122 on hESC differentiation, using genomewide gene microarrays. Stable overexpression of endoderm-specific miR-122 in hESC resulted in increased expression of a few endodermal markers in spontaneously-differentiating hESC, but had no clear effect on directing differentiation towards an endodermal fate; rather, it delayed the general differentiation of hESC. Experiment Overall Design: Lentiviral vectors encoding either wt or mutant (control) hsa-miR-122 were transduced into hES cells (line HES2). The cells differentiated spontaneously in KO medium without feeder cells for 2 weeks, and the gene expression profile of wt- vs mutant-expressing miR-122 was compared. We used for this study 3 arrays for control (mutant miR) and 2 arrays for the treatment (wt miRNA).

2008-11-15 | E-GEOD-13460 | biostudies-arrayexpress

Molecular Insights into Non-teratoma-forming Induced Pluripotent Stem Cells

2012-04-30 | GSE31970 | GEO

Directed differentiation of oligodendrocytes from human embryonic stem cells

Project description:Here we compare the transcriptional profile of the undifferentiated hESC with the anterior oligodendroctes derived from the hESC using our new differentiation protocol. Total RNA was isolated from undifferentiated hES cells and from hES derived oligodendrocytes, 70 days old and FACS sorted for O4 marker. Samples for each group in triplicate were processed for Illumina bead arrays (Illumina HT-12) by the MSKCC genomics core facility according to the specifications of the manufacturer.

2015-02-01 | E-GEOD-63318 | biostudies-arrayexpress

Transcriptional landscape changes during human embryonic stem cell derivation

Project description:Currently, there is only minimal information elucidating the transcriptional changes occurring during the in vitro transition of the inner cell mass (ICM) towards the human embryonic stem cell (hESC) stage and the role played by the post inner cell mass intermediate (PICMI). In this study, we perform in-depth analysis of the transcriptional heterogeneity between these three stages of hESC derivation in order to correlate their downstream effects on pluripotency states and differentiation. We reveal that although PICMI is transcriptionally in close proximity to the hESC profile and distinct from ICM, it exhibits upregulation of primordial germ cell markers, dependence on LIF signaling, upregulation of naïve pluripotency-specific signaling networks and appears to be a switching point from naïve to primed pluripotency. This indicates similarities with mouse epiblast-like cells displaying a transient state of pluripotency, between naïve and primed pluripotent states. Overall, we highlight the need to gain insight into the molecular and transcriptional landscape during hESC derivation, which will further help in the derivation of human PGCs and naïve hESCs in vitro which remains inefficient.

2018-09-24 | GSE119378 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data