Teratoma formation is the gold standard assay for testing the capacity of human stem cells to differentiate into all embryonic germ layers. Although widely used, little effort has been made to transform this qualitative assay into a quantitative one. Using gene expression data from a wide variety of cells, we created a gene scorecard representing tissues from all three germ layers as well as an extraembryonic tissue. A calculated grade using this gene list successfully distinguishes pluripotent stem cell-initiated teratomas from malignant tumors, thereby translating cell potency into a quantitative measure. This new methodology, named TeratoScore, thus assesses the pluripotency of human cells, and is easily performed using an open-source code. The new teratoma database also allowed us to examine the gene expression differences between tumors with a diploid karyotype and those initiated by aneuploid cells. We found that while teratomas originating from aneuploid cells pass the TeratoScore benchmark for pluripotency, they exhibit aberrant gene expression congruent with human chromosomal syndromes (such as Down syndrome). This gene expression signature is significantly different from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, suggesting aberrant teratomas may be beneficial for in vivo disease modeling. Teratoma formation followed by TeratoScore analysis can rapidly assess cell potency and allows comparison between different pluripotent cell lines.
TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas.
Cell line
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Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
Sex, Age
View SamplesHuman pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is the trisomy of chromosome 12. Interestingly, trisomy 12 is also prevalent in germ cell tumors (GCTs). Here, we aimed to dissect the cellular and molecular implications of trisomy 12 in hPSCs. A genome-wide gene expression analysis revealed that trisomy 12 profoundly affects the global gene expression profile of hPSCs, inducing a transcriptional program very similar to that of CGTs. Direct comparison of the proliferation, replication, differentiation and apoptosis between diploid and aneuploid hPSCs revealed that trisomy 12 significantly increases the proliferation rate of hPSCs. Increased replication largely accounts for the increased proliferation observed, and may explain the selection advantage that trisomy 12 confers to hPSCs. A comparison of the tumors induced by diploid and aneuploid hPSCs further demonstrated that trisomy 12 increases the tumorigenicity of hPSCs, inducing transcriptionally-distinct teratomas, from which pluripotent cells can be recovered. Lastly, a chemical screen of 89 anticancer drugs against diploid and aneuploid hPSCs discovered that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors, suggesting that the increased proliferation and tumorigenicity of these aberrant cells also makes them more vulnerable, and might potentially be used for their selective elimination from culture. Together, our findings demonstrate the extensive effect of trisomy 12 on the gene expression signature and on the cellular behavior of hPSCs, and highlight the danger posed by this trisomy for the successful use of hPSCs in basic research and in regenerative medicine.
Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells.
Specimen part, Cell line
View SamplesTransgenic rice plants expressing isopentenyltransferase (IPT), an enzyme that catalyzes the rate-limiting step in CK synthesis under the control of SARK, a maturation- and stress-inducible promoter. Increased CK production resulted in sink source alteration and enhanced drought tolerance of the transgenic plants.
Cytokinin-mediated source/sink modifications improve drought tolerance and increase grain yield in rice under water-stress.
Age, Specimen part
View SamplesCLK targets from fly heads using the TIM-GAL4; UAS-CLKGR line
Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component.
No sample metadata fields
View SamplesDown syndrome (DS) is the leading genetic cause of mental retardation and is caused by a third copy of human chromosome 21. The different pathologies of DS involve many tissues with a distinct array of neural phenotypes. Here we characterize new embryonic stem cell lines with DS (DS-ESCs), and focus on the neural aspects of the diease. Our results show that neural progenitor cells (NPCs) differentiated from five independent DS-ESC lines display increased apoptosis and down-regulation of forehead developmental genes. Analysis of differentially expressed genes suggested RUNX1 as a key transcription regulator in DS-NPCs. Using genome editing we were able to disrupt all three copies of RUNX1 in DS-ESCs, leading to down-regulation of several RUNX1 target developmental genes accompanied by reduced apoptosis and neuron migration. Our work sheds new light on the role of RUNX1 and the importance of dosage balance in the development of neural phenotypes in DS.
Molecular Characterization of Down Syndrome Embryonic Stem Cells Reveals a Role for RUNX1 in Neural Differentiation.
Sex, Specimen part
View SamplesDue to their somatic cell origin, human induced pluripotent stem cells (HiPSCs) are assumed to carry a normal diploid genome, and adaptive chromosomal aberrations have not been fully evaluated. Here, we analyzed the chromosomal integrity of 66 HiPSC and 38 human embryonic stem cell (HESC) samples from 18 different studies by global gene expression meta-analysis. We report identification of a substantial number of cell lines carrying full and partial chromosomal aberrations, half of which were validated at the DNA level. Several aberrations resulted from culture adaptation, and others are suspected to originate from the parent somatic cell. Our classification revealed a third type of aneuploidy already evident in early passage HiPSCs, suggesting considerable selective pressure during the reprogramming process. The analysis indicated high incidence of chromosome 12 duplications, resulting in significant enrichment for cell cycle related genes. Such aneuploidy may limit the differentiation capacity and increase the tumorigenicity of HiPSCs.
Identification and classification of chromosomal aberrations in human induced pluripotent stem cells.
Specimen part, Cell line
View SamplesInrauterine growth restriction was induced by chronic hyper insulinemia in pregnant rats and differential gene expression was studied using affymetrix rat genome RAE230A.Data was analysed using SAM.
Adult hypertension in intrauterine growth-restricted offspring of hyperinsulinemic rats: evidence of subtle renal damage.
No sample metadata fields
View Samples6 Timepoint microarray from control strain
Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component.
No sample metadata fields
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