Filters
Technology
Platform
GSE31458
Mus musculus
29 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
PD is the second most common neurodegenerative disease worldwide with growing prevalence. MPTP is a neurotoxin which causes the appearance of Parkinson's disease (PD) pathology. The involvement of the cholinergic system in PD has been identified decades ago and anti-cholinergic drugs were upon the first drugs used for symptomatic treatment of PD. Of note, MPTP intoxication is a model of choice for symptomatic neuroprotective therapies since it have been quite predictive. Mice were exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), with or without the protective acetylcholinesterase (AChE-R) variant. Transgenic AChE-S (the synaptic variant), AChE-R (the shorter, protective variant) and FVB/N control mice were included in this study. Two brain regions were examined: the pre-frontal cortex (PFC) and the striatal caudate-putamen (CPu). Each condition (i.e brain region and transgenic variant) was examined on both naive and MPTP-exposed mice.
Publication Title
Meta-analysis of genetic and environmental Parkinson's disease models reveals a common role of mitochondrial protection pathways.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
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.
Publication Title
MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The tumorigenicity of human pluripotent stem cells (hPSCs) is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a specific cell surface marker of hPSCs that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for hPSC survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and clostridium perfringens enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of hPSC-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated hPSCs from culture, highlighting a strategy that may increase the safety of hPSC-based cell therapies.
Publication Title
Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Pluripotent-specific inhibitors (PluriSIns) make a powerful tool for studying the mechanisms that control the survival of human pluripotent stem cells (hPSCs). Here we characterize PluriSIn#2 as a novel selective indirect inhibitor of topoisomerase II alpha (TOP2A). We find that TOP2A is uniquely expressed in undifferentiated hPSCs, and that its inhibition results in their rapid cell death. These findings reveal a dependency of hPSCs on the activity of TOP2A, which can be harnessed for their selective elimination from culture.
Publication Title
Brief reports: Controlling the survival of human pluripotent stem cells by small molecule-based targeting of topoisomerase II alpha.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human pluripotent stem cells (hPSCs) tend to acquire chromosomal aberrations in culture, which may increase their tumorigenicity. However, the cellular mechanism(s) underlying these aberrations are largely unknown. Here we show that the DNA replication in aneuploid hPSCs is perturbed, resulting in high prevalence of defects in chromosome condensation and segregation. Global gene expression analyses in aneuploid hPSCs revealed decreased levels of actin cytoskeleton genes and their common transcription factor SRF. Down-regulation of SRF or chemical perturbation of actin cytoskeleton organization in diploid hPSCs resulted in increased replication stress and perturbation of chromosome condensation, recapitulating the findings in aneuploid hPSCs. Altogether, our results revealed that in hPSCs DNA replication stress results in a distinctive defect in chromosome condensation, underlying their ongoing chromosomal instability. Our results shed a new light on the mechanisms leading to ongoing chromosomal instability in hPSCs, and may be relevant to tumor development as well.
Publication Title
Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Clariom S Pico Assay HT (clariomshumanht)
Description
Human CD4+CD45RA+CD25- cells were lentivirally transduced with wild-type or mutated (A384T or R397W) FOXP3, or an empty vector (EV). Transduced cells were sorted 14 days post-transduction based on GFP expression, and were restimulated with soluble anti-CD3 (30 ng/mL) and irradiated PBMCs (3x) for 14 more days. Cells were then activated with 0.5 g/ml of phytohemagglutinin (PHA) in the presence or absence of SGF003 (8 g/mL), and total RNA was extracted for microarray analysis. Overall, this study highlights the functional impact of TIP60 in FOXP3-driven Treg biology and provides a novel target for manipulation of human Treg activity.
Publication Title
Suppression by human FOXP3<sup>+</sup> regulatory T cells requires FOXP3-TIP60 interactions.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human ESCs are pluripotent cells that have the capacity of self renewal for a prolonged period in vitro, and can differentiate into derivatives of all three primary germ layers: endoderm, mesoderm and ectoderm. Human ESCs are responsive to a wide range of factors in vitro that can direct their differentiation into specific cell types. We analyzed the effect of nicotinamide (NIC) on differentiation of hESCs in vitro. CEL file for GSM424319 is unavailable.
Publication Title
Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Recently, a frequent chromosomal aberration fusing Androgen regulated TMPRSS2 promoter and the ERG gene (T/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between the T/ERG and other defective pathways in cancer progression however, the biological mechanism by which the T/ERG operates is yet to be determined. Using immortalized prostate epithelial cells (EP) model we were able to show that EP with the combination of androgen receptor(AR) and T/ERG(EP-AR T/ERG cell line) demonstrate an Epithelial to Mesenchymal Transition (EMT) manifested by a mesenchyme-like morphological appearance and behavior.
Publication Title
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Due 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.
Publication Title
Identification and classification of chromosomal aberrations in human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Due 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.
Publication Title
Identification and classification of chromosomal aberrations in human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples