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GSE11889
Homo sapiens
45 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We found that composition of cell subsets within the CD34+ cell population is markedly altered in chronic phase (CP) chronic myeloid leukemia (CML). Specifically, proportions and absolute cell counts of common myeloid progenitors (CMP) and megakaryocyte-erythrocyte progenitors (MEP) are significantly greater in comparison to normal bone marrow whereas absolute numbers of hematopoietic stem cells (HSC) are equal. To understand the basis for this, we performed gene expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets from six patients with CP CML and five healthy donors. Euclidean distance analysis revealed a remarkable transcriptional similarity between the CML patients' HSC and normal progenitors, especially CMP. CP CML HSC were transcriptionally more similar to their progeny than normal HSC to theirs, suggesting a more mature phenotype. Hence, the greatest differences between CP CML patients and normal donors were apparent in HSC including downregulation of genes encoding adhesion molecules, transcription factors, regulators of stem-cell fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and migratory capacities were functionally corroborated by fibronectin detachment analysis and transwell assays, respectively. Based on our findings we propose a loss of quiescence of the CML HSC on detachment from the niche leading to expansion of myeloid progenitors.
Publication Title
The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. Genomic profiling of distinct HSPC subsets revealed a consistent deregulation of signaling cascades, including TGF beta signaling, p38MAPK signaling and pathways involved in cytoskeletal organization, migration, adhesion and cell cycle regulation in MM patients.
Publication Title
Multiple myeloma-related deregulation of bone marrow-derived CD34(+) hematopoietic stem and progenitor cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Twist1 is a transcription factor that induces EMT and drives metastasis in prostate cancer. We examined global gene expression in Myc-CaP mouse prostate cancer cells following overexpression
Publication Title
The twist box domain is required for Twist1-induced prostate cancer metastasis.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 13 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge.
Publication Title
Methamphetamine preconditioning alters midbrain transcriptional responses to methamphetamine-induced injury in the rat striatum.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
We performed the whole transcriptome analysis in Zscan4 positive ES cells (Em+) and Zscan4 negative ES cells (Em-) by using FACS-sorted MC1-ZE7 ES cells. Overall design: Whole RNA-seq in Zscan4 positive and negative cells
Publication Title
Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Overall design: Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.
Publication Title
Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Age-related frailty may in part be due to a decreased competency in skeletal muscle regeneration. The role of the closely related TGFbeta amily molecules myostatin and GDF11 in regeneration is unclear. The commercially available antibody which in a prior report was used to demonstrate an age-related decrease in GDF11 was found to detect both GDF11 and myostatin, and with this reagent it appears that the combination of GDF11 and myostatin increases with age in serum. Mechanistically, GDF11 and myostatin induce SMAD2/3 phosphorylation, and both inhibit myoblast differentiation and regulate identical downstream signaling. GDF11 injected into adult mice in a model of regeneration induces an increase in smaller fibers and a decrease in satellite cell expansion. There are no signs of benefit from GDF11 to regeneration. Thus, GDF11 appears to be an age-associated myokine that inhibits muscle differentiation, and is thus a target for blockade to treat frailty
Publication Title
GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.
Sample Metadata Fields
Treatment, Time
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
GPAM is well characterized in triglyceride synthesis, but has never been implicated in cancer. Our study report a role for GPAM in cell migration. Gene expression changes after GPAM silencing was investigated to gain insight into possible mechanisms underlying GPAM's role in cell migration.
Publication Title
Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
With this study we wanted to evaluate the impact of murine norovirus infection of germfree mice and to compare it to germfree mice which have received fecal transplants of conventional mice. Overall design: whole small intestinal tissue analysis of 3 germfree, 3 germfree mice infected with murine norovirus and 3 conventionalized germfree mice
Publication Title
An enteric virus can replace the beneficial function of commensal bacteria.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 449 Downloadable Samples
- Illumina HiSeq 4000
Description
Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounds such as passaging effects and progenitor storage. Single cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility. Overall design: RNAseq profiles of 57 bulk Human iPSC-Derived Neurons differentiated across five laboratories were generated in triplicates at two different time points and sequenced on 1 lane of HiSeq4000 at 75bp paired end. RNAseq profiles of .... single cells extracted from 2 of the 5 laboratories at the later time point were isolated by FACS onto 96-well plates and sequenced on 1 lane of HiSeq4000 at 75bp paired end.
Publication Title
Reproducibility of Molecular Phenotypes after Long-Term Differentiation to Human iPSC-Derived Neurons: A Multi-Site Omics Study.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples